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Zhou X, Huang X, Zhou L, Zou Y. Recurrent ischemic stroke with patent foramen ovale linked to seronegative antiphospholipid syndrome: a case report and literature review. Front Immunol 2025; 16:1558309. [PMID: 40242764 PMCID: PMC12000043 DOI: 10.3389/fimmu.2025.1558309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 03/13/2025] [Indexed: 04/18/2025] Open
Abstract
The disability and mortality rates of recurrent ischemic stroke tend to be higher than those of the first stroke, which seriously affects the quality of life and prognosis of patients. Accurately identifying the etiology of stroke is critical for guiding effective treatment, and one of the most noteworthy in young patients is antiphospholipid syndrome (APS). Despite the progress made in APS research, seronegative APS (SN-APS) remains underdiagnosed. We present a case of recurrent ischemic stroke accompanied by PFO, which is associated with SN-APS. A 49-year-old female presented with expressive dysphasia and unresponsiveness on October 4, 2022. The magnetic resonance imaging (MRI) of cerebral revealed left frontal lobe infarcts; neither magnetic resonance angiography (MRA) nor magnetic resonance venography (MRV) showed significant hemodynamic stenosis or venous thrombosis. Subsequently, she was admitted to global aphasia and right hemiparesis and treated with intravenous thrombolysis and PFO closure on July 21, 2023. 9 months later, on April 23, 2024, she had a recurrence of ischemic stroke and tested negative for conventional antiphospholipid antibodies (aPL). However, the livedo reticularis on the inner side of the patient's feet triggered our in-depth investigations and reflections. Due to the presence of positive non-criteria antibodies, the patient was eventually diagnosed with SN-APS and received standardized antithrombotic therapy. Our report suggests stroke can be a major manifestation of SN-APS, and a comprehensive evaluation by rheumatology and neurology teams is crucial to recognize it early. Prompt diagnosis and early anticoagulation therapy are beneficial to the prognosis of patients.
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Affiliation(s)
| | | | | | - Yongbiao Zou
- Department of Neurology, The Central Hospital of Shaoyang, Shaoyang, Hunan, China
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Yang L, Guo R, Liu H, Chen B, Li C, Liu R, Liao S, Xie Q, Yin G. Mechanism of antiphospholipid antibody-mediated thrombosis in antiphospholipid syndrome. Front Immunol 2025; 16:1527554. [PMID: 40181965 PMCID: PMC11966034 DOI: 10.3389/fimmu.2025.1527554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 02/25/2025] [Indexed: 04/05/2025] Open
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of thrombotic or obstetrical events in patients with persistent antiphospholipid antibodies (aPL). Thrombotic events, the primary pathological hallmarks and clinical manifestations, are among the leading causes of mortality in APS. Our understanding of the mechanism underlying APS-related thrombosis has significantly advanced in recent years. The presence of aPL, particularly anti-β2-glycoprotein I (anti-β2GPI) antibodies, is a major driver of thrombosis. The proposed pathophysiological mechanisms of aPL-mediated pro-thrombotic events can be broadly categorized into three types: disruption of anticoagulant reactions and fibrinolysis, interference with coagulation cascade cells, and complement activation. A triggering 'second hit' is typically necessary to initiate thrombosis. The development of animal models of APS has further refined our understanding of the role of aPL in thrombosis. In this review, we focused on the role of β2GPI-dependent aPL in thrombosis of thrombotic APS.
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Affiliation(s)
- Leiyi Yang
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Ruibing Guo
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Hongjiang Liu
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Chen
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Changpei Li
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Ruiting Liu
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Shuyi Liao
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Qibing Xie
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Geng Yin
- Health Management Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, China
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Akankwasa P, Kakooza J, Katongole J, Namutosi E, Lewis C, Okurut E. Antiphospholipid syndrome in pregnancy: A comprehensive review. World J Rheumatol 2025; 12:103837. [DOI: 10.5499/wjr.v12.i2.103837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/17/2025] [Accepted: 01/23/2025] [Indexed: 02/18/2025] Open
Abstract
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by the presence of antiphospholipid antibodies and is associated with thrombotic events and pregnancy complications. The classification and management of APS has evolved over time. The classification criteria for APS include laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic domains. Management focuses on prevention of thrombotic events and/or anticoagulation as the primary treatment for thrombosis. Postpartum and long-term thromboprophylaxis after delivery are recommended to reduce the risk of thrombotic events. Despite these recommendations, optimal anticoagulation agents and intensity of treatment are still topics of debate. Further research is needed to understand the pathophysiology of APS and improve its management during pregnancy. In this review, we discuss the classification and pathophysiology of APS. Current treatment options and clinical trials are also discussed.
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Affiliation(s)
- Prosper Akankwasa
- Department of Obstetrics and Gynecology, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
| | - Jackson Kakooza
- Department of Surgery, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
| | - John Katongole
- Department of Obstetrics and Gynecology, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
| | - Esther Namutosi
- Department of Obstetrics and Gynecology, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
| | - Catherine Lewis
- Department of Surgery, St. Joseph's Kitovu Hospital, Masaka, Uganda
- Department of Surgery, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States
| | - Emmanuel Okurut
- Department of Obstetrics and Gynecology, Kampala International University Western Campus, Ishaka Bushenyi, Uganda
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Murray A, Campbell EJ, Clarke AE, Barber MRW, Pannu T, Fritzler MJ, Jung M, St. Pierre Y, Skeith L. Non-criteria antiphospholipid antibody profiles and thrombotic outcomes in a cohort of patients with systemic lupus erythematosus. Lupus Sci Med 2024; 11:e001174. [PMID: 39672566 PMCID: PMC11647292 DOI: 10.1136/lupus-2024-001174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 11/12/2024] [Indexed: 12/15/2024]
Abstract
OBJECTIVES Antiphospholipid syndrome (APS) is characterised by the presence of antiphospholipid antibodies (aPLs) and clinical outcomes of thrombosis and/or obstetric morbidity and is associated with systemic lupus erythematosus (SLE). IgG antiphosphatidylserine/prothrombin complex (aPS/PT), IgM aPS/PT and IgG anti-beta 2 glycoprotein 1-domain 1 (aβ2GP1-D1) are novel aPLs that have been associated with thrombosis; however, conclusive data are still lacking. It remains unclear how best to incorporate non-criteria autoantibodies into clinical decision-making. The aim of this study was to assess whether these novel aPLs were associated with an increased risk of thrombosis in patients with SLE. METHODS We evaluated 341 patients enrolled in the SouThern Alberta Registry for Lupus EryThematosus database with SLE by the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria. Medical records were reviewed between March 2006 and January 2021 for thrombotic events and serology results for lupus anticoagulant, IgG anticardiolipin, IgG anti-beta 2 glycoprotein 1 (aβ2GP1), IgG aPS/PT, IgM aPS/PT and IgG aβ2GP1-D1. RESULTS Among 341 patients with SLE, 59 (17%) met the revised Sapporo lab criteria, and of those 29 (49%) had a major thrombotic event (OR 3.5, 95% CI 1.9 to 6.3). Among 142 patients who had at least one positive non-criteria autoantibody, 45 (32%) had a major thrombotic event (OR 1.6, 95% CI 0.97 to 2.6). In a univariate analysis, the IgG aPS/PT and IgG aβ2GP1-D1 were associated with major and all thrombotic events. In a multivariate analysis that controlled for age, sex, prednisone use, SLE disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K and the revised Sapporo lab criteria, among the non-criteria aPLs, only IgG aPS/PT was associated with an increased risk of a major thrombosis (OR 2.2, 95% CI 1.1 to 4.5). CONCLUSIONS In our multivariate analysis, IgG aPS/PT was associated with a modestly increased risk of thrombotic events.
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Affiliation(s)
- Alistair Murray
- Division of Hematology and Hematologic Malignancies, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Eric J Campbell
- Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Ann Elaine Clarke
- Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Megan R W Barber
- Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Tania Pannu
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Marvin J Fritzler
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Michelle Jung
- Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Yvan St. Pierre
- Division of Clinical Epidemiology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Leslie Skeith
- Division of Hematology and Hematologic Malignancies, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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Truglia S, Riitano G, Mancuso S, Recalchi S, Rapino L, Garufi C, Manganelli V, Garofalo T, Misasi R, Alessandri C, Sorice M, Longo A, Conti F, Capozzi A. Antibody profiles in the mosaic of 'seronegative' APS syndrome. Clin Exp Immunol 2024; 218:275-282. [PMID: 39192704 PMCID: PMC11557137 DOI: 10.1093/cei/uxae079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 07/15/2024] [Accepted: 08/23/2024] [Indexed: 08/29/2024] Open
Abstract
Clinical manifestations, as distinct from thrombotic and obstetric morbidity, were recently included in the update of classification criteria of the antiphospholipid syndrome (APS). However, the existence of several patients with clinical manifestations suggestive of APS, but negative for criteria antiphospholipid antibodies (aPLs) [anti-cardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2-GPI), and lupus anticoagulant] may suggest an update of diagnostic criteria. In this study, we analysed the prevalence of six non-criteria aPLs in a large monocentric cohort of patients with seronegative APS (SN-APS), to investigate their possible diagnostic role. aCL IgA, aβ2-GPI IgA, and aβ2-GPI Domain 1 antibodies were detected by chemiluminescence, anti-phosphatidylserine/prothrombin (aPS/PT) IgG, anti-vimentin/cardiolipin (aVim/CL) IgG, and anti-carbamylated-β2-glycoprotein I (aCarb-β2-GPI) IgG by ELISA in sera from 144 SN-APS patients. In SN-APS patients, aCL IgA was detected in 4/144 (2.77%), aβ2-GPI IgA in 2/144 (1.39%), aβ2-GPI-Domain 1 in 1/144 (0.69%), aPS/PT in 16/144 (11.11%), aVim/CL in 37/144 (25.69%), and aCarb-β2-GPI in 43/144 patients (29.86%). Patients negative for all non-criteria aPL assays were 77/144 (53.47%). Notably, the Venn diagram showed that aCarb-β2-GPI together with aVim/CL represented the prevalent combination of positive antibodies. In SN-APS patients, aCL IgA were associated with recurrent thrombosis (OR 11.48; P = 0.03); in obstetric SN-APS patients, aPS/PT were significantly associated with foetal deaths (OR 4.84; P = 0.01), aVim/CL with spontaneous abortions (OR 2.71; P = 0.016). This study indicates that aPS/PT, aVim/CL and aCarb-β2-GPI antibodies may represent useful tools to identify 'seronegative' APS patients, who are negative for criteria aPLs, supporting the need to make testing for non-criteria aPLs more accessible in patients with SN-APS.
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Affiliation(s)
- Simona Truglia
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche Cardiovascolari, Sapienza University, Rome, Italy
| | - Gloria Riitano
- Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy
| | - Silvia Mancuso
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche Cardiovascolari, Sapienza University, Rome, Italy
| | - Serena Recalchi
- Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy
| | - Luca Rapino
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche Cardiovascolari, Sapienza University, Rome, Italy
| | - Cristina Garufi
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche Cardiovascolari, Sapienza University, Rome, Italy
| | | | - Tina Garofalo
- Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy
| | - Roberta Misasi
- Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy
| | - Cristiano Alessandri
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche Cardiovascolari, Sapienza University, Rome, Italy
| | - Maurizio Sorice
- Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy
| | - Agostina Longo
- Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy
| | - Fabrizio Conti
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche Cardiovascolari, Sapienza University, Rome, Italy
| | - Antonella Capozzi
- Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy
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Mısırcı S, Ekin A, Yağız B, Coşkun BN, Dalkılıç E, Pehlivan Y. The Validation of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria in a Cohort from Turkey. Diagnostics (Basel) 2024; 14:2205. [PMID: 39410609 PMCID: PMC11476238 DOI: 10.3390/diagnostics14192205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 09/25/2024] [Accepted: 10/01/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND/OBJECTIVES Our aim was to validate the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for antiphospholipid syndrome (APS), published in 2023, in an APS cohort. METHODS A total of 193 patients, 83 with APS (secondary APS, n = 45; primary APS, n = 38) and 110 without APS (systemic lupus erythematosus (SLE), n = 100; others, n = 10), were included in this study. The performance (sensitivity, specificity and area under the curve (AUC)) of the 2023 ACR/EULAR classification criteria for APS was evaluated and the agreement with the revised Sapporo criteria was compared using the kappa test. RESULTS In our cohort, the sensitivity and specificity of the 2023 ACR/EULAR classification criteria for APS were 73% and 94%, respectively (AUC: 0.836, 95% CI: 0.772-0.899), while the sensitivity and specificity of the revised Sapporo criteria were 66% and 98%, respectively (95% CI: 0.756-0.888). The performance of the two sets of criteria in our cohort was significantly consistent and significant (p < 0.001). When the sensitivity, specificity and ROC curve analysis were performed again by excluding livedo racemosa, the sensitivity of the new criteria in our cohort was 62% and the specificity was 100% (AUC: 0.813, 95% CI: 0.746-0.881). CONCLUSIONS Although the newly published criteria broaden the scope of APS classification by including clinical findings other than thrombosis and obstetric criteria, their sensitivity in our cohort was low. On the other hand, we found that the specificity of the criteria in our cohort reached 100% when livedo findings were excluded.
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Affiliation(s)
- Salim Mısırcı
- Department of Internal Medicine, Division of Rheumatology, Faculty of Medicine, Bursa Uludag University, 16059 Bursa, Turkey; (A.E.); (B.Y.); (B.N.C.); (E.D.); (Y.P.)
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Qadir NA, Cargill M, Choudhry H, Rai O, Desai P, Lamsal S, Reddy P. Seronegative Catastrophic Antiphospholipid Syndrome: A Case Report of a Deadly Diagnosis. Cureus 2024; 16:e70785. [PMID: 39493117 PMCID: PMC11531318 DOI: 10.7759/cureus.70785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 10/03/2024] [Indexed: 11/05/2024] Open
Abstract
Catastrophic antiphospholipid syndrome (CAPS) is a rare autoimmune condition that causes diffuse hypercoagulability affecting multiple organ systems. Typically, CAPS is diagnosed via serological workup, clinical findings, or histopathological findings. However, patients with clinical features of CAPS have been found to be seronegative. This case report aims to inform clinicians of the growing array of CAPS serological markers and the need for further research into these markers to assess clinical viability. Here, we present a case of a 51-year-old female who presented with multi-system thrombosis and was diagnosed with seronegative CAPS (SN-CAPS). Given the significant mortality rate associated with CAPS, it is imperative that an early diagnosis is established, and treatment is initiated. Thus, continued serological research for CAPS is required to aid in this effort.
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Affiliation(s)
- Nadim A Qadir
- Internal Medicine, University of Florida College of Medicine - Jacksonville, Jacksonville, USA
| | - Michael Cargill
- Internal Medicine, University of Florida College of Medicine - Jacksonville, Jacksonville, USA
| | - Hamza Choudhry
- Internal Medicine, University of Florida College of Medicine - Jacksonville, Jacksonville, USA
| | - Oshin Rai
- Internal Medicine, University of Florida College of Medicine - Jacksonville, Jacksonville, USA
| | - Parth Desai
- Internal Medicine, University of Florida College of Medicine - Jacksonville, Jacksonville, USA
| | - Sanjay Lamsal
- Radiology, University of Florida College of Medicine - Jacksonville, Jacksonville, USA
| | - Pramod Reddy
- Internal Medicine, University of Florida College of Medicine - Jacksonville, Jacksonville, USA
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8
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Mancuso S, De Michele M, Truglia S, Capozzi A, Rapino L, Berto I, Alessandri C, Toni D, Manganelli V, Sorice M, Conti F. Cryptogenic stroke and seronegative antiphospholipid syndrome: a case series of patients with positivity for "non-criteria" antiphospholipid antibodies. Reumatismo 2024; 76. [PMID: 39324554 DOI: 10.4081/reumatismo.2024.1701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 05/23/2024] [Indexed: 09/27/2024] Open
Abstract
Cerebrovascular events (CE) are one of the most common and severe events in antiphospholipid syndrome (APS), a condition characterized by thrombosis and circulating anti-phospholipid antibodies (aPL). Seronegative APS (SN-APS) refers to a group of patients with clinical features of APS but persistently negative tests for "criteria aPL": anti-cardiolipin antibodies (aCL) and anti-β2glycoprotein I antibodies detected by enzyme-linked immunosorbent assay (ELISA), and the lupus anticoagulant detected by clotting assays. We report a series of five cases of SN-APS in young or middle-aged patients who tested positive for "non-criteria" aPL. We retrospectively collected cases of SN-APS patients who experienced CE without an identified cause despite an extensive diagnostic work-up and tested negative for criteria aPL. All the patient sera were tested for aCL by immunostaining on thin-layer chromatography (TLC) and anti-vimentin/cardiolipin (aCL/Vim) by ELISA. We identified five cases of female patients aged 21 to 58 years, evaluated at the Rheumatology Unit and/ or Stroke Unit/Emergency Department of the Sapienza University Hospital of Rome, "Policlinico Umberto I". All patients presented a clinical history suggestive of APS. All the patients tested positive for aCL by TLC-immunostaining, and one patient was positive for aCL/Vim. In young or middle-aged patients with cryptogenic CE and a clinical history suggestive of APS, the use of new diagnostic tools for identifying aPL, if validated in future studies, could represent an important step in the prompt diagnosis of APS.
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Affiliation(s)
- S Mancuso
- Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome
| | - M De Michele
- Stroke Unit, Emergency Department, "Sapienza" University of Rome
| | - S Truglia
- Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome
| | - A Capozzi
- Department of Experimental Medicine, "Sapienza" University of Rome
| | - L Rapino
- Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome
| | - I Berto
- Stroke Unit, Emergency Department, "Sapienza" University of Rome
| | - C Alessandri
- Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome
| | - D Toni
- Stroke Unit, Emergency Department, "Sapienza" University of Rome
| | - V Manganelli
- Department of Experimental Medicine, "Sapienza" University of Rome
| | - M Sorice
- Department of Experimental Medicine, "Sapienza" University of Rome
| | - F Conti
- Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome
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9
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Aguirre Del-Pino R, Monahan RC, Huizinga TWJ, Eikenboom J, Steup-Beekman GM. Risk Factors for Antiphospholipid Antibodies and Antiphospholipid Syndrome. Semin Thromb Hemost 2024; 50:817-828. [PMID: 38228166 DOI: 10.1055/s-0043-1776910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Persistence of serum antiphospholipid antibodies (aPL) is associated with a high thrombotic risk, both arterial and venous, and with pregnancy complications. Due to the potential morbidity and mortality associated with the presence of aPL, identifying and recognizing risk factors for the development of aPL and thrombosis in aPL carriers may help to prevent and reduce the burden of disease. Multiple elements are involved in the pathomechanism of aPL development and aPL-related thrombosis such as genetics, malignancy, and infections. This review will address the role of both well-known risk factors and their evolution, and of emerging risk factors, including COVID-19, in the development of aPL and thrombosis in aPL carriers.
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Affiliation(s)
- Rodrigo Aguirre Del-Pino
- Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
- Division of Rheumatology, A Coruña University Hospital (CHUAC), Galicia, Spain
| | - Rory C Monahan
- Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
- Department of Clinical Epidemiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Tom W J Huizinga
- Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Jeroen Eikenboom
- Division of Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Gerda M Steup-Beekman
- Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
- Department of Rheumatology, Haaglanden Medical Center, The Hague, The Netherlands
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10
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Khamashta M, Hughes GRV. Hughes syndrome: The discovery of the antiphospholipid syndrome. Med Clin (Barc) 2024; 163 Suppl 1:S1-S3. [PMID: 39174147 DOI: 10.1016/j.medcli.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/12/2024] [Accepted: 04/15/2024] [Indexed: 08/24/2024]
Abstract
In the 40 years since the original detailed description of antiphospholipid syndrome (APS), the condition has come to be regarded as one of the most common autoimmune diseases. The impact of the description has been enormous - for example, the recognition that some individuals with connective tissue diseases require anticoagulation rather than corticosteroids or anti-inflammatory treatment has bought about fundamental change in medical practice. In obstetrics, APS is now regarded as the most important prothrombotic cause of recurrent pregnancy loss - with pregnancy success improving from below 20% to current live birth rate over 80%. In neurology, APS may be associated with up to 20% of strokes in people under 40 - a striking figure not least in terms of medical economics, let alone in potentially preventable suffering. In vascular medicine, APS links immunology with thrombosis and vascular disease and may well provide insights into immunological factors in the pathogenesis of atherosclerosis.
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Affiliation(s)
- Munther Khamashta
- Emeritus Professor of Medicine, King's College London, GSK Global Medical Expert-Lupus, Dubai, United Arab Emirates.
| | - Graham R V Hughes
- Emeritus Professor of Rheumatology, King's College London, The London Lupus & Rheumatology Centre, London, United Kingdom
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11
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Celia AI, Galli M, Mancuso S, Alessandri C, Frati G, Sciarretta S, Conti F. Antiphospholipid Syndrome: Insights into Molecular Mechanisms and Clinical Manifestations. J Clin Med 2024; 13:4191. [PMID: 39064231 PMCID: PMC11277906 DOI: 10.3390/jcm13144191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 07/12/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Antiphospholipid syndrome (APS) is a complex systemic autoimmune disorder characterized by a hypercoagulable state, leading to severe vascular thrombosis and obstetric complications. The 2023 ACR/EULAR guidelines have revolutionized the classification and understanding of APS, introducing broader diagnostic criteria that encompass previously overlooked cardiac, renal, and hematologic manifestations. Despite these advancements, diagnosing APS remains particularly challenging in seronegative patients, where traditional tests fail, yet clinical symptoms persist. Emerging non-criteria antiphospholipid antibodies offer promising new diagnostic and management avenues for these patients. Managing APS involves a strategic balance of cardiovascular risk mitigation and long-term anticoagulation therapy, though the use of direct oral anticoagulants remains contentious due to varying efficacy and safety profiles. This article delves into the intricate pathogenesis of APS, explores the latest classification criteria, and evaluates cutting-edge diagnostic tools and therapeutic strategies.
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Affiliation(s)
- Alessandra Ida Celia
- Rheumatology, Department of Clinical Internal, Anesthesiological e Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy; (A.I.C.); (S.M.); (C.A.); (F.C.)
| | - Mattia Galli
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (G.F.); (S.S.)
- Maria Cecilia Hospital, GVM Care & Research, 48033 Cotignola, Italy
| | - Silvia Mancuso
- Rheumatology, Department of Clinical Internal, Anesthesiological e Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy; (A.I.C.); (S.M.); (C.A.); (F.C.)
| | - Cristiano Alessandri
- Rheumatology, Department of Clinical Internal, Anesthesiological e Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy; (A.I.C.); (S.M.); (C.A.); (F.C.)
| | - Giacomo Frati
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (G.F.); (S.S.)
- IRCCS Neuromed, 86077 Pozzilli, Italy
| | - Sebastiano Sciarretta
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (G.F.); (S.S.)
- IRCCS Neuromed, 86077 Pozzilli, Italy
| | - Fabrizio Conti
- Rheumatology, Department of Clinical Internal, Anesthesiological e Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy; (A.I.C.); (S.M.); (C.A.); (F.C.)
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Feng W, Qiao J, Tan Y, Liu Q, Wang Q, Yang B, Yang S, Cui L. Interaction of antiphospholipid antibodies with endothelial cells in antiphospholipid syndrome. Front Immunol 2024; 15:1361519. [PMID: 39044818 PMCID: PMC11263079 DOI: 10.3389/fimmu.2024.1361519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 06/19/2024] [Indexed: 07/25/2024] Open
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disease with arteriovenous thrombosis and recurrent miscarriages as the main clinical manifestations. Due to the complexity of its mechanisms and the diversity of its manifestations, its diagnosis and treatment remain challenging issues. Antiphospholipid antibodies (aPL) not only serve as crucial "biomarkers" in diagnosing APS but also act as the "culprits" of the disease. Endothelial cells (ECs), as one of the core target cells of aPL, bridge the gap between the molecular level of these antibodies and the tissue and organ level of pathological changes. A more in-depth exploration of the relationship between ECs and the pathogenesis of APS holds the potential for significant advancements in the precise diagnosis, classification, and therapy of APS. Many researchers have highlighted the vital involvement of ECs in APS and the underlying mechanisms governing their functionality. Through extensive in vitro and in vivo experiments, they have identified multiple aPL receptors on the EC membrane and various intracellular pathways. This article furnishes a comprehensive overview and summary of these receptors and signaling pathways, offering prospective targets for APS therapy.
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Affiliation(s)
- Weimin Feng
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
- Institute of Medical Technology, Health Science Centre, Peking University, Beijing, China
| | - Jiao Qiao
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
- Institute of Medical Technology, Health Science Centre, Peking University, Beijing, China
| | - Yuan Tan
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
- Institute of Medical Technology, Health Science Centre, Peking University, Beijing, China
| | - Qi Liu
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
- Institute of Medical Technology, Health Science Centre, Peking University, Beijing, China
| | - Qingchen Wang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Boxin Yang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Shuo Yang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Liyan Cui
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
- Institute of Medical Technology, Health Science Centre, Peking University, Beijing, China
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Yang Y, Jiang H, Tang Z, Pan H, Liu H, Cheng X, Su Y, Ye J, Hu Q, Meng J, Chi H, Zhou Z, Jia J, Yang C, Shi H, Teng J, Liu T. Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice. J Autoimmun 2024; 146:103237. [PMID: 38749076 DOI: 10.1016/j.jaut.2024.103237] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 02/08/2024] [Accepted: 02/12/2024] [Indexed: 09/18/2024]
Abstract
OBJECTIVES To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aβ2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.
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Affiliation(s)
- Yaqing Yang
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haiyue Jiang
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zihan Tang
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haoyu Pan
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Honglei Liu
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaobing Cheng
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yutong Su
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junna Ye
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiongyi Hu
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianfen Meng
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huihui Chi
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhuochao Zhou
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinchao Jia
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chengde Yang
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hui Shi
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jialin Teng
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingting Liu
- Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Zahidin MA, Iberahim S, Hassan MN, Zulkafli Z, Mohd Noor NH. Clinical and Laboratory Diagnosis of Antiphospholipid Syndrome: A Review. Cureus 2024; 16:e61713. [PMID: 38975541 PMCID: PMC11225094 DOI: 10.7759/cureus.61713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/05/2024] [Indexed: 07/09/2024] Open
Abstract
The antiphospholipid syndrome (APS) manifests through venous or arterial thrombosis, with or without pregnancy complication alongside the continuous presence of antiphospholipid antibodies (aPL). APS classification relies on three aPL subtypes: anticardiolipin (aCL), anti-β2-glycoprotein I antibodies (anti-β2GPI), and lupus anticoagulants (LA) antibodies. Given that thrombosis and pregnancy issues are not unique to APS, the precise and reliable identification of aPL forms the basis for diagnosis. Semi-quantitative solid-phase assays identify two antibodies, aCL and anti-β2GPI, while LA detection occurs through various phospholipid-dependent coagulation assays that are based on antibody behaviour. LA, specifically, is conclusively associated with thrombosis, prompting discussions around the serological criteria for APS. Despite advancements in LA detection, the standardisation of all aPL detection assays remains imperative. The combined presence of aCL and anti-β2GPI with thrombosis inconsistently triggers concern. Initial presentations by APS patients commonly exhibit a heightened risk of stroke, miscarriages in the later stages of pregnancy, positive results of LA tests, and widespread thrombosis across multiple organs, often leading to adverse outcomes. Correctly diagnosing this condition is pivotal to avoid unnecessary long-term secondary thromboprophylaxis.
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Affiliation(s)
- Muhamad Aidil Zahidin
- Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, MYS
| | - Salfarina Iberahim
- Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, MYS
| | - Mohd Nazri Hassan
- Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, MYS
| | - Zefarina Zulkafli
- Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, MYS
| | - Noor Haslina Mohd Noor
- Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, MYS
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Akyüz Dağlı P, Erden A, Babaoğlu H, Karakaş Ö, Özdemir Ulusoy B, Konak HE, Armağan B, Erten Ş, Omma A. Non-criteria autoantibodies in antiphospholipid syndrome may be associated with underlying disease activity. Ir J Med Sci 2024; 193:1099-1107. [PMID: 37737913 DOI: 10.1007/s11845-023-03519-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 09/04/2023] [Indexed: 09/23/2023]
Abstract
BACKGROUND Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by persistent antiphospholipid antibodies (aPLs) with arterial and venous thrombosis and/or pregnancy morbidity. In recent years, several studies have highlighted the potential role of non-criteria aPL in diagnosing APS patients. AIM This study aimed to determine the association of the presence of non-criteria aPL antibodies to the clinical and laboratory features of patients with a diagnosis of APS. METHODS Eighty patients diagnosed with APS and under observation in the rheumatology clinic of Ankara City Hospital were assessed. Patient demographic and clinical features were meticulously recorded. Non-criteria antibodies tested in our center included antiphosphatidylserine IgA, antiphosphatidylserine IgM, beta 2 glycoprotein IgA, anti-cardiolipin IgA, antiphospholipid antibody IgG, and antiphospholipid antibody IgM. Antibodies from patients who were tested for at least one non-criteria antibody were documented. RESULTS Out of 80 patients, 55 (68.8%) were tested for at least one non-criteria antibody, and 29 of those patients (52.7%) tested positive for at least one non-criteria antibody. The antiphospholipid antibody IgM and the beta 2 glycoprotein IgA were the most commonly tested non-criteria antibodies. Patients with non-criteria antibody positivity had a higher frequency of Ds DNA positivity and low complement (62.0% vs. 35.0%, p = 0.042; 69.0% vs. 38.0%, p = 0.023), respectively. In addition, positivity for anti-cardiolipin IgG and b2 glycoprotein IgG was significantly higher in the group positive for non-criteria antibodies (79% vs. 31%, p ≤ 0.001; 72.0% vs. 19%, p ≤ 0.001). There was no significant difference between the clinical features of patients with at least one positivity for non-criteria antibodies and those without. CONCLUSION Systemic lupus erythematosus (SLE) is the most commonly associated disease with APS, being present in approximately 35% of cases [1]. Since the majority of the patient group in our study had APS that was secondary to SLE, non-criteria antibody positivity may be linked to the immunological activity of SLE. Large multicenter studies are necessary to investigate the clinical significance of isolated/combined positivity for criterion/non-criteria aPLs.
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Affiliation(s)
| | - Abdulsamet Erden
- Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
- Gazi University Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Ankara, Turkey
| | - Hakan Babaoğlu
- Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | - Özlem Karakaş
- Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | | | | | - Berkan Armağan
- Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | - Şükran Erten
- Ankara Yıldırım Beyazıt University Medical School, Department of Internal Medicine, Division of Rheumatology, Ankara City Hospital, Ankara, Turkey
| | - Ahmet Omma
- University of Health Sciences, Ankara City Hospital, Department of Internal Medicine, Division of Rheumatology, Ankara City Hospital, Ankara, Turkey
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Li S, Zhao J, Bai Y, Meng J, Wang Q, Tian X, Li M, Zeng X, Hu C. Profile and clinical relevance of non-criteria antiphospholipid antibodies in patients diagnosed with or highly suspected of APS. Rheumatology (Oxford) 2024; 63:891-900. [PMID: 37382568 DOI: 10.1093/rheumatology/kead303] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 05/09/2023] [Accepted: 06/06/2023] [Indexed: 06/30/2023] Open
Abstract
OBJECTIVE This study investigates the positivity and relevance of non-criteria aPLs with clinical phenotypes in patients highly suspected of or diagnosed with APS. METHODS Outpatient cases were included from a prospectively maintained database, and patients were grouped into APS (n = 168), seronegative APS (SNAPS, n = 9), those meeting the diagnostic criteria for clinical events without laboratory results (only-event, n = 15), those that had aPL positivity without clinical manifestations (asymptomatic APA, n = 39), and healthy controls (n = 88). Criteria aPL results and APS-related clinical features were extracted. Sixteen non-criteria aPLs were tested and analysed. RESULTS LA, aCL and anti-β2 glycoprotein-I were positive in 84.5%, 61.3% and 74.4% of APS patients, and 61.5%, 59.0% and 74.4% of asymptomatic APA patients, respectively. In patients negative for criteria serological tests, 23 out of 24 were positive for at least one non-criteria aPL. Triple-positive patients also had significantly higher tests of some aPLs in comparison with other groups. Stroke was associated with anti-phosphatidyl-inositol (aPI) IgG and anti-phosphatidyl-glycerol (aPG) IgG. Late embryonic loss correlated with aPI IgM, and premature birth/eclampsia was associated with aPI IgG and aPG IgG. There were also positive associations between heart valve lesions and anti-phosphatidylserine-prothrombin (aPS/PT) IgM, APS nephropathy and anti-phosphatidyl-choline IgG or aPS/PT IgG, and livedo reticularis and anti-phosphatidyl-ethanolamine IgM. CONCLUSION The prevalence of non-criteria aPLs differed from diagnostic biomarkers in patients diagnosed with or suspected of APS. Detection of aPLs provided additive value in the evaluation of APS-related clinical manifestations.
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Affiliation(s)
- Siting Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Jiulang Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Yina Bai
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Jingjing Meng
- Department of Clinical Laboratory, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qian Wang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xinping Tian
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Chaojun Hu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
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Qiao J, Bailly J, Opie J. Key Issues at the Forefront of Diagnosis and Testing for Antiphospholipid Syndrome. Clin Appl Thromb Hemost 2024; 30:10760296241306751. [PMID: 39692090 DOI: 10.1177/10760296241306751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2024] Open
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by antiphospholipid antibodies associated with thrombosis and pregnancy complications. Catastrophic APS is a severe form involving multiple organ systems with a high mortality rate. The pathogenesis involves antiphospholipid antibodies which target phospholipid-binding proteins and damage endothelial cells thus activating coagulation, triggering a pro-thrombotic state. Laboratory tests for antiphospholipid antibody detection include lupus anticoagulant testing in the coagulation laboratory and serological detection of anticardiolipin and anti-beta 2 glycoprotein I antibodies. Despite recent updates in the diagnostic criteria for APS the recent decades and our improved knowledge of this disease, there remain several key issues pertaining to diagnosis and testing with potential implications to patient management. Here we briefly review APS pathophysiology, strengths and weaknesses of classification criteria, laboratory challenges leading to test interpretation, and clinical management of this complex condition.
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Affiliation(s)
- Jesse Qiao
- Department of Pathology and Laboratory Medicine, University of California, Irvine, USA
| | - Jenique Bailly
- Division of Haematology, Department of Pathology, University of Cape Town and National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa
| | - Jessica Opie
- Division of Haematology, Department of Pathology, University of Cape Town and National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa
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Radin M, Barinotti A, Cecchi I, Foddai SG, Rubini E, Roccatello D, Menegatti E, Sciascia S. Thrombin generation assay and lupus anticoagulant synergically distinguish populations of patients with antiphospholipid antibodies. J Clin Pathol 2023; 76:839-846. [PMID: 36100400 DOI: 10.1136/jcp-2022-208199] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 08/30/2022] [Indexed: 11/04/2022]
Abstract
AIM To apply thrombin generation assay (TGA) in a large cohort of antiphospholipid antibodies (aPL)-positive patients. MATERIAL AND METHODS 108 patients were tested with TGA and lupus anticoagulant (LA) testing and divided according to their aPL profile. Briefly, 21 patients were positive for anti-phosphatidylserine (aPS)/prothrombin (PT) IgG/IgM (group1), 29 for anti-ß2-glycoprotein-I (aβ2GPI) and anti-cardiolipin (aCL) IgG/IgM (group2), 31 for aPS/PT, aβ2GPI and aCL IgG/IgM (group3), 27 for aPS/PT and/or aβ2GPI+aCL IgM at low-titres (group4). 31 healthy donors (HDs) and 24 controls treated with vitamin K antagonists (VKA) were included. RESULTS The most deranged TGA and LA profiles were observed in tetra-positive patients (group3) that differed significantly to the other groups, thus those with isolated, double or triple aPL-positivity. Moreover, when comparing the TGA profile of all antiphospholipid syndrome (APS) patients, aPL-carriers, HDs and VKA controls, we observed that the aPL+ patients (especially APS) showed a distinctive profile that allowed to distinguish them from the other groups with significantly higher tLag and tPeak, and lower Peak and area under the curve.When focusing on APS clinical manifestations, patients with a high-risk profile (group3) showed significant differences from those presenting low-titres aPL (group 4) regarding the number of venous events (p=0.04), recurrence of any thrombotic event (p=0.01), of arterial events (5 vs 0, p=0.02), the occurrence of TIA (p=0.04), DVT (p=0.02) and, when analysing extracriteria manifestations, of peripheral artery disease (p=0.04). CONCLUSIONS TGA seems a valuable approach to stratify aPL+ patients according to their risk profile. The differences among different populations of autoantibodies specificities could be considered a translational validation of the increased thrombotic risk of patients with triple or tetra aPL-positivity.
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Affiliation(s)
- Massimo Radin
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
| | - Alice Barinotti
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
| | - Irene Cecchi
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
| | - Silvia Grazietta Foddai
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
| | - Elena Rubini
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
| | - Dario Roccatello
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
| | - Elisa Menegatti
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- School of Specialization of Clinical Pathology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Savino Sciascia
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy
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19
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Ding Z, Pan H, Yang Z, Yang C, Shi H. Beyond the classics: The emerging value of anti-phosphatidylserine/prothrombin antibodies in antiphospholipid syndrome. Clin Immunol 2023; 256:109804. [PMID: 37838215 DOI: 10.1016/j.clim.2023.109804] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 09/24/2023] [Accepted: 10/05/2023] [Indexed: 10/16/2023]
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs), which can lead to thrombosis and pregnancy complications. Within the diverse range of aPLs, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) have gained significance in clinical practice. The detection of aPS/PT has proven valuable in identifying APS patients and stratifying their risk, especially when combined with other aPL tests like lupus anticoagulant (LA) and anti-β2-glycoprotein I (aβ2GPI). Multivariate analyses have confirmed aPS/PT as an independent risk factor for vascular thrombosis and obstetric complications, with its inclusion in the aPL score and the Global Anti-Phospholipid Syndrome Score (GAPSS) aiding in risk evaluation. However, challenges remain in the laboratory testing of aPS/PT, including the need for assay standardization and its lower sensitivity in certain patient populations. Further research is necessary to validate the clinical utility of aPS/PT antibodies in APS diagnosis, risk stratification, and management.
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Affiliation(s)
- Zetao Ding
- Department of Rheumatology and Immunology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Haoyu Pan
- Department of Rheumatology and Immunology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhixia Yang
- Department of Rheumatology and Immunology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chengde Yang
- Department of Rheumatology and Immunology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Shi
- Department of Rheumatology and Immunology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
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Kuchar O, Petrackova M, Kalousova M, Noskova L, Zima T, Fialova L. Levels and avidities of antiphosphatidylethanolamine antibodies in patients with thrombotic events and immunologically-mediated diseases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2023; 167:254-262. [PMID: 35147138 DOI: 10.5507/bp.2022.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 01/25/2022] [Indexed: 11/23/2022] Open
Abstract
AIMS Antiphosphatidylethanolamine antibodies (aPE) represent one type of antiphospholipid antibody (aPL) directed against the neutral phospholipids - phosphatidylethanolamines. The aim of this study was to evaluate levels and avidities of aPE in several groups of patients and compare them with conventional aPLs. METHODS aPE were analysed in a cohort consisting of 68 hospitalized patients. The other cohort comprised 22 patients with immunologically-mediated diseases. The control group consisted of 20 healthy persons. ELISA methods were used for determination of aPL. Avidities of aPE were tested by modified ELISA with urea as a chaotropic agent. RESULTS aPE IgG/IgM were significantly higher in the group of patients with venous thromboembolism than those with non-thrombotic internal disorders (P=0.02 for both Ig classes). aPE IgG/IgM elevated above cut-off values were found in 10.8% of patients with venous thromboembolism and as a single aPL in 6.5%. Levels of aPE IgG higher than our limit (>6 U/mL) were detected in 29% of patients with immunologically-mediated diseases with other positive aPL. Low-, intermediate- and high-avidity aPE IgG were found in patients of both cohorts. The avidities of aPE IgG differed from those of anticardiolipin antibodies IgG. Neither aPE IgG levels nor avidity dynamics significantly changed during follow-up. CONCLUSION aPE may be related to venous thromboembolism and may be part of the repertoire of aPL in immunologically-mediated diseases. There are patients with thrombosis negative for conventional aPL but positive for aPE. aPE IgG may have different avidities.
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Affiliation(s)
- Oliver Kuchar
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
- Thomayer University Hospital, Czech Republic
| | - Milada Petrackova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Marta Kalousova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Libuse Noskova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Tomas Zima
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Lenka Fialova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
- Department of Health Care and Population Protection, Faculty of Biomedical Engineering, Czech Technical University in Prague, Czech Republic
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Mayer-Pickel K, Nanda M, Gajic M, Cervar-Zivkovic M. Preeclampsia and the Antiphospholipid Syndrome. Biomedicines 2023; 11:2298. [PMID: 37626793 PMCID: PMC10452741 DOI: 10.3390/biomedicines11082298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 08/06/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies (aPLs). Preeclampsia complicates about 10-17% of pregnancies with APS. However, only early onset preeclampsia (<34 weeks of gestation) belongs to the clinical criteria of APS. The similarities in the pathophysiology of early onset preeclampsia and APS emphasize an association of these two syndromes. Overall, both are the result of a defective trophoblast invasion and decidual transformation at early gestation. Women with APS are at increased risk for prematurity; the reasons are mostly iatrogenic due to placental dysfunction, such as preeclampsia or FGR. Interestingly, women with APS have also an increased risk for preterm delivery, even in the absence of FGR and preeclampsia, and therefore it is not indicated but spontaneous. The basic treatment of APS in pregnancy is low-dose aspirin and low-molecular-weight heparin. Nevertheless, up to 20-30% of women develop complications at early and late gestation, despite basic treatment. Several additional treatment options have been proposed, with hydroxychloroquine (HCQ) being one of the most efficient. Additionally, nutritional interventions, such as intake of vitamin D, have shown promising beneficial effects. Curcumin, due to its antioxidant and anti-inflammatory properties, might be considered as an additional intervention as well.
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Affiliation(s)
- Karoline Mayer-Pickel
- Department of Obstetrics, Medical University Graz, 8036 Graz, Austria; (M.N.); (M.G.); (M.C.-Z.)
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Caraiola S, Voicu L, Jurcut C, Dima A, Baicus C, Baicus A, Cobilinschi CO, Ionescu RA. Criteria and Non-Criteria Antiphospholipid Antibodies in Antiphospholipid Syndrome: How Strong Are They Correlated? Biomedicines 2023; 11:2192. [PMID: 37626689 PMCID: PMC10452164 DOI: 10.3390/biomedicines11082192] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/27/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023] Open
Abstract
The place of non-criteria antiphospholipid antibodies (aPLs) in the diagnosis of antiphospholipid syndrome (APS) is still debatable. The aim of this research was to evaluate the correlations between the titres of non-criteria aPLs (anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and anti-prothrombin (aPT) antibodies), and the ones of the already studied criteria aPLs (anti-cardiolipin (aCL) and anti-β2 glycoprotein I-aβ2GPI antibodies). Altogether, 72 APS (30 primary and 42 secondary) patients were included in our study. High correlation coefficients (rs) were found between aPS IgM and aCL IgM, overall (0.77, p < 0.01), as well as in the primary (0.81, p < 0.01), and secondary (0.75, p < 0.01) APS subgroups. Low or statistically insignificant correlations were observed between IgG/IgM isotypes of aPT and aCL, or aβ2GPI, in the entire study population, and when evaluating the subgroups. Therefore, moderate correlations were mainly identified between the tested non-criteria antibodies and the criteria ones, suggesting little added value for the use of the tested non-criteria aPLs, with the exception of aPT, which seems to have different kinetics and might be a promising APS diagnostic tool.
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Affiliation(s)
- Simona Caraiola
- Fifth Department-Internal Medicine (Cardiology, Gastroenterology, Hepatology, Rheumatology, Geriatrics), Family Medicine, Occupational Medicine, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Internal Medicine Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Laura Voicu
- Internal Medicine Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Ciprian Jurcut
- Internal Medicine Department, “Dr. Carol Davila” Central University Emergency Military Hospital, 010825 Bucharest, Romania
| | - Alina Dima
- Rheumatology Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Cristian Baicus
- Fifth Department-Internal Medicine (Cardiology, Gastroenterology, Hepatology, Rheumatology, Geriatrics), Family Medicine, Occupational Medicine, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Internal Medicine Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Anda Baicus
- Fifth Department-Internal Medicine (Cardiology, Gastroenterology, Hepatology, Rheumatology, Geriatrics), Family Medicine, Occupational Medicine, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Laboratory Department, The University Emergency Hospital, 050098 Bucharest, Romania
| | - Claudia Oana Cobilinschi
- Fifth Department-Internal Medicine (Cardiology, Gastroenterology, Hepatology, Rheumatology, Geriatrics), Family Medicine, Occupational Medicine, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Rheumatology Department, “Sf. Maria” Clinical Hospital, 011172 Bucharest, Romania
| | - Razvan Adrian Ionescu
- Fifth Department-Internal Medicine (Cardiology, Gastroenterology, Hepatology, Rheumatology, Geriatrics), Family Medicine, Occupational Medicine, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Internal Medicine Department, Colentina Clinical Hospital, 020125 Bucharest, Romania
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Liu Q, Yang S, Tan Y, Cui L. High-throughput sequencing technology facilitates the discovery of novel biomarkers for antiphospholipid syndrome. Front Immunol 2023; 14:1128245. [PMID: 37275905 PMCID: PMC10235516 DOI: 10.3389/fimmu.2023.1128245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 05/09/2023] [Indexed: 06/07/2023] Open
Abstract
Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis and/or morbid pregnancy, accompanied by persistent antiphospholipid antibody (aPL) positivity. However, due to the complex pathogenesis of APS and the large individual differences in the expression of aPL profiles of patients, the problem of APS diagnosis, prognosis judgment, and risk assessment may not be solved only from the antibody level. It is necessary to use new technologies and multiple dimensions to explore novel APS biomarkers. The application of next-generation sequencing (NGS) technology in diseases with a high incidence of somatic mutations, such as genetic diseases and tumors, has been very mature. Thus, we try to know the research and application progress of APS by NGS technology from genome, transcriptome, epigenome and other aspects. This review will describe the related research of NGS technology in APS and provide more reference for the deep understanding of APS-related screening markers and disease pathogenesis.
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Affiliation(s)
- Qi Liu
- Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China
- Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China
- Institute of Medical Technology, Peking University Health Science Center, Beijing, China
| | - Shuo Yang
- Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China
- Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Yuan Tan
- Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China
- Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China
- Institute of Medical Technology, Peking University Health Science Center, Beijing, China
| | - Liyan Cui
- Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China
- Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China
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Peng X, Tan X, Xing A. An advanced understanding of the heterogeneous clinical features of "non-criteria" obstetric antiphospholipid syndrome: Two case reports and a literature review. Front Immunol 2023; 14:1122127. [PMID: 36865564 PMCID: PMC9971720 DOI: 10.3389/fimmu.2023.1122127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 01/31/2023] [Indexed: 02/16/2023] Open
Abstract
Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by recurrent venous and/or arterial thrombosis and/or pregnancy complications, in the presence of elevated antiphospholipid (aPL) antibodies. APS in pregnant women is referred to as "obstetrical" APS (OAPS). The diagnosis of definite OAPS requires the presence of one or more typical clinical criteria and persistent aPL antibodies at least 12 weeks apart. However, the classification criteria for OAPS have generated wide discussion, with a growing impression that certain patients not fully meeting these criteria might be inappropriately excluded from the classification, which is known as "non-criteria" OAPS. We present here two unique cases of potentially lethal "non-criteria" OAPS, complicating severe preeclampsia, fetal growth restriction (FGR), liver rupture, preterm birth, refractory recurrent miscarriages, or even stillbirth. We further share our diagnostic search and analysis, treatment adjustment, and prognosis for this unusual antenatal event. We will also present a short review of an advanced understanding of the pathogenetic mechanisms of this disease, heterogeneous clinical features, and potential significance.
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Affiliation(s)
- Xue Peng
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Xi Tan
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Aiyun Xing
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
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Li S, Bai Y, Meng J, Wang Q, Tian X, Li M, Zeng X, Zhao J, Hu C. Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients. Front Immunol 2023; 14:1107510. [PMID: 37122726 PMCID: PMC10132625 DOI: 10.3389/fimmu.2023.1107510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 03/30/2023] [Indexed: 05/02/2023] Open
Abstract
Background The presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the diagnostic value of a set of non-criteria aPLs and their relevance with APS-related criteria and extra-criteria manifestations. Methods From a prospectively constructed database, consecutive APS patients consisting of 114 primary APS (PAPS group), 54 with APS secondary to SLE (SAPS group), 9 seronegative APS (SNAPS), as well as 209 patients with systemic lupus erythematosus (SLE) and 88 healthy controls were included in this study. Levels of criteria aPLs, baseline information, and APS-related criteria and extra-criteria features were extracted from the database. Serum levels of non-criteria aPLs including aPC IgG/IgM, aPI IgG/IgM, aPE IgG/IgM/IgA, aPG IgG/IgM/IgA, anti-phosphatidic acid (aPA) IgG/IgM, aSM IgG/IgM, and aPS/PT IgG/IgM were analyzed with AESKULISA® ELISA Test Kits. Results The addition of aPC IgG/M, aPI IgG/M, aPE IgG/M/A, aSM IgG/M, and aPA IgG/M to aCL or aβ2GPI IgG/M could significantly increase diagnostic sensitivity and accuracy. A significant difference between PAPS or SAPS and HC was presented in all non-criteria aPLs except for aSM IgM and aPG IgA. Eight out of nine SNAPS patients were positive for at least 1 aPL. Pregnancy morbidity was associated with aSM IgM (r = 0.22) and aSM IgG (r = 0.15). Pre-eclampsia or premature birth was associated with aSM IgG (r = 0.16), aPI IgG (r = 0.22), aPC IgG (r = 0.16), and aPG IgG (r = 0.18). Stroke was associated with aPI IgG (r = 0.2). The clinical association was also observed in DVT with aPS/PT IgG (r = 0.17). Valve lesion was positively associated with aSM IgM (Fisher test p = 0.039), APS nephropathy was associated with aPC IgG (OR 3.797), and livedo reticularis was associated with aPE IgM (OR 15.391). Conclusion Additional detection of non-criteria aPLs including aPC IgG/M, aPE IgG/M/A, aPI IgG/M, aSM IgG/M, and aPA IgG/M could assist in APS diagnosis. The positivity of certain aPLs was statistically associated with both criteria and extra-criteria APS clinical manifestations.
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Affiliation(s)
- Siting Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Yina Bai
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Jingjing Meng
- Department of Clinical Laboratory, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qian Wang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xinping Tian
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Jiuliang Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
- *Correspondence: Chaojun Hu, ; Jiuliang Zhao,
| | - Chaojun Hu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
- *Correspondence: Chaojun Hu, ; Jiuliang Zhao,
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Liu X, Zhu L, Liu H, Cai Q, Yun Z, Sun F, Jia Y, Guo J, Li C. Non-criteria antiphospholipid antibodies in antiphospholipid syndrome: Diagnostic value added. Front Immunol 2022; 13:972012. [PMID: 36389827 PMCID: PMC9643638 DOI: 10.3389/fimmu.2022.972012] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/03/2022] [Indexed: 11/22/2022] Open
Abstract
Objective Non-criteria antiphospholipid antibodies (aPLs) increase the diagnostic value for antiphospholipid syndrome (APS) and contribute to better recognition of seronegative APS (SNAPS). However, the clinical utility and the diagnostic value of non-criteria aPLs are inconsistent. This study aimed to investigate the prevalence and clinical significance of 7 non-criteria aPLs in a large APS cohort. Methods Seven non-criteria aPLs, including anti-phosphatidylserine/prothrombin (aPS/PT) antibodies IgG/IgA/IgM, anti-phosphatidylethanolamine antibodies (aPE) IgG/IgA/IgM, anti-Annexin V antibodies (aAnnexinV) IgG/IgA/IgM, anti-phosphatidylserine antibodies (aPS) IgM, aPS IgG, antibodies directed against a mixture of phospholipids (APhL) IgG, and APhL IgM were tested among 175 patients with APS, 122 patients with other autoimmune diseases (as disease controls), and 50 healthy controls. Results In the present study, the highest prevalence of non-criteria aPLs was seen in aAnnexinV (58.86%). APhL IgG and aPS IgM showed the highest specificity (95.35%) and aPS/PT showed the highest Youden index (0.3991) for the diagnostic value of APS. The aAnnexinV also showed the highest prevalence in SNAPS (43.3%), followed by APhL IgM (21.7%), aPE (16.7%) and aPS/PT (16.7%). APhL IgG, aPS/PT, and aPS IgG showed positive association with thrombotic events in APS patients [APhL IgG: odds ratio (OR) = 2.26, 95% confidence interval (CI) 1.18-4.34, p = 0.013; aPS/PT: OR = 2.48, 95% CI: 1.32-4.69, p = 0.004; aPS IgG: OR = 1.90, 95% CI 1.01-3.60, p = 0.046; respectively). The inclusion of the non-criteria aPLs increased the accuracy of APS diagnosis from 65.7% to 87.4%. Conclusion Our data provide evidence that adding the non-criteria aPLs can improve the diagnostic accuracy in APS. APhL IgG, aPS/PT, and aPS IgG may be potential biomarkers to predict the risk of thrombosis in APS.
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Affiliation(s)
- Xiangjun Liu
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
| | - Lei Zhu
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
- Department of Clinical Laboratory, Affiliated Nantong Rehabilitation Hospital of Nantong University, Nantong, China
| | - Hongjiang Liu
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
| | - Qingmeng Cai
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
| | - Zelin Yun
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
| | - Feng Sun
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
| | - Yuan Jia
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
| | - Jianping Guo
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
| | - Chun Li
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
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Hubben A, McCrae KR. Emerging Therapies in Antiphospholipid Syndrome. Transfus Med Rev 2022; 36:195-203. [PMID: 36272841 PMCID: PMC10162403 DOI: 10.1016/j.tmrv.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 09/14/2022] [Accepted: 09/15/2022] [Indexed: 11/15/2022]
Abstract
The antiphospholipid syndrome (APS) is the most common cause of acquired immune-mediated thrombophilia. This syndrome is broadly defined by the presence of arterial or venous thrombosis, or pregnancy morbidity, in the presence of high levels of antiphospholipid antibodies. Despite recognition of this disorder more than 50 years ago, a fundamental unifying pathogenesis has not been determined. Due to this, mechanism-based therapies for APS are not available, and current management following thrombotic events suggests anticoagulation of indeterminate duration, or for obstetric complications, heparin/low molecular weight heparin and aspirin. However, APS is an autoimmune disorder, and several approaches focused on modulating the immune response or its effectors have been employed. Those which have been most extensively studied include hydroxychloroquine, rituximab and eculizumab, an inhibitor of complement C5. In this report, we review in depth, and critique, key clinical studies of these agents. Since all of these studies are small, our conclusions are qualified. However, it appears that hydroxychloroquine may enhance the anticoagulant efficacy of vitamin K antagonists in APS patients, and that rituximab may ameliorate some of the "non-criteria" manifestations of APS. The catastrophic antiphospholipid syndrome (CAPS) is associated with diffuse thrombosis, multi-organ dysfunction, and ∼30% mortality. A high incidence of complement regulatory gene mutations, and compelling data concerning the efficacy of eculizumab in CAPS, suggests an important role for complement in this disorder. However, additional work is needed to clarify the role of complement in non-catastrophic APS, though emerging data suggests that complement inhibition may be effective in preventing thrombosis in these patients as well.
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Affiliation(s)
- Anne Hubben
- Department of Cardiovascular and Metabolic Sciences, Taussig Cancer Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Keith R McCrae
- Department of Cardiovascular and Metabolic Sciences, Taussig Cancer Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
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Chandra MS, G A M, M RK. Primary Sjögren's Syndrome Presenting as Cerebral Venous Thrombosis: A Rare Case. Cureus 2022; 14:e28772. [PMID: 36225515 PMCID: PMC9531848 DOI: 10.7759/cureus.28772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2022] [Indexed: 11/18/2022] Open
Abstract
Sjogren’s syndrome is a late-onset, slowly progressing autoimmune disease characterized by the destruction of the exocrine glands by lymphocytic infiltration, resulting in dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). Sjögren's syndrome may be associated with various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. We report a case of a 34-year-old female who delivered a live baby 20 days ago. She presented in a postictal state after two episodes of tonic-clonic movements of limbs with altered sensorium with a history of headache for seven days. Further evaluation revealed that the subject had a history of multiple abortions and grittiness in her eyes. MRI showed signs of infarction in the left parietal lobe and magnetic resonance venography (MRV) suggested cavernous venous thrombosis. After an unwavering effort to rule out alternate causes, the rare correlation between primary Sjogren’s syndrome and cerebral venous thrombosis was considered. Additional investigations were performed, which showed the patient to be positive for Anti SS-A (Ro52), Anti SS-B (La), and anti-centromere antibodies. The patient gradually improved with anti-edema measures and steroids and was discharged by day nine. We present this case to emphasize the neurological manifestation of Sjogren’s syndrome, which may present as cerebral venous thrombosis.
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Pires da Rosa G, Ferreira E, Sousa-Pinto B, Rodríguez-Pintó I, Brito I, Mota A, Cervera R, Espinosa G. Comparison of non-criteria antiphospholipid syndrome with definite antiphospholipid syndrome: A systematic review. Front Immunol 2022; 13:967178. [PMID: 36059460 PMCID: PMC9434011 DOI: 10.3389/fimmu.2022.967178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Objectives Patients with laboratory or clinical manifestations suggestive of antiphospholipid syndrome (APS) but not fulfilling the classification criteria constitute a clinical challenge. This study aims to compare non-criteria APS (NC-APS) with definite APS in terms of clinical manifestations, therapies, and outcomes. Methods A systematic review of observational studies comparing definite and NC-APS was performed searching four electronic databases. Data on clinical manifestations, therapies and clinical outcomes was extracted. Results Sixteen studies, assessing a total of 3,798 participants, were included. Seven out of 10 studies found no significant difference in the prevalence of arterial or venous thrombosis between definite and NC-APS, with two studies on seronegative APS also finding no difference in thrombosis recurrence. Seven out of 12 studies found no significant difference in the prevalence of obstetric manifestations between groups, with the remaining exhibiting conflicting results. In 9 studies comparing treatment frequency in obstetric patients, all but one described similar treatment frequency, with the percentage of NC-APS treated during pregnancy ranging from 26% to 100%. In 10 studies comparing pregnancy outcomes of NC-APS versus definite APS, 7 found similar successful pregnancies/live births. Additionally, 5 studies described improvement of live births in both groups with treatment, with three signalling aspirin monotherapy as efficacious as combination therapy in NC-APS. Conclusion This review hints at an absence of marked differences in most evaluated parameters between definite and NC-APS, emphasizing the value of a more active follow-up of these patients. The low-quality available evidence highlights the need for well-defined NC-APS populations in future studies. Systematic Review Registration https://www.crd.york.ac.uk/prospero, identifier CRD42020210674.
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Affiliation(s)
- Gilberto Pires da Rosa
- Department of Autoimmune Diseases, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- Department of Dermatovenereology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine, University of Porto, Porto, Portugal
| | - Ester Ferreira
- Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Internal Medicine, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Bernardo Sousa-Pinto
- MEDCIDS – Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal
- CINTESIS – Center for Health Technology and Services Research, Porto, Portugal
| | | | - Iva Brito
- Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Rheumatology, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Alberto Mota
- Department of Dermatovenereology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Ricard Cervera
- Department of Autoimmune Diseases, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Gerard Espinosa
- Department of Autoimmune Diseases, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
- *Correspondence: Gerard Espinosa,
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Lenti MV, Rossi CM, Melazzini F, Gastaldi M, Bugatti S, Rotondi M, Bianchi PI, Gentile A, Chiovato L, Montecucco C, Corazza GR, Di Sabatino A. Seronegative autoimmune diseases: A challenging diagnosis. Autoimmun Rev 2022; 21:103143. [PMID: 35840037 DOI: 10.1016/j.autrev.2022.103143] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/10/2022] [Indexed: 12/19/2022]
Abstract
Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren's syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.
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Affiliation(s)
- Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Carlo Maria Rossi
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Federica Melazzini
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Matteo Gastaldi
- Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy
| | - Serena Bugatti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Unit of Rheumatology, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Mario Rotondi
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
| | - Paola Ilaria Bianchi
- Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Antonella Gentile
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Luca Chiovato
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
| | - Carlomaurizio Montecucco
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Unit of Rheumatology, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Gino Roberto Corazza
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy.
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Kim HS, Lee ES, Shin BS, Kang HG. Recurrent Cerebral Artery Dissection Associated with Seronegative Antiphospholipid Antibody Syndrome. Tomography 2022; 8:754-759. [PMID: 35314639 PMCID: PMC8938765 DOI: 10.3390/tomography8020062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 11/16/2022] Open
Abstract
Stroke in young patients requires thorough evaluation as they often lack risk factors. Antiphospholipid syndrome can cause arterial thrombosis and pregnancy loss; hence, differential diagnoses should include seronegative antiphospholipid syndrome. We report a case of recurrent ischemic stroke caused by recurrent dissection in a patient with a history of pregnancy loss. A 33-year-old woman was admitted with global aphasia and right hemiparesis. During intra-arterial thrombectomy, a left middle cerebral artery dissection was detected. After 5.5 years, she was re-admitted for dysarthria, left facial palsy, subtle left hemiparesis, and right middle cerebral artery dissection. She tested negative for autoimmune diseases and vasculitis. However, underlying pathologic conditions could not be excluded because of the unique disease course. Finally, she was diagnosed with seronegative antiphospholipid syndrome. The concept of seronegative antiphospholipid syndrome has been proposed for patients with clinical features suggestive of antiphospholipid syndrome but with negative titers. However, this syndrome can only be diagnosed by exclusion. Furthermore, arterial dissection should be considered to be its main pathology. Antiphospholipid syndrome itself can be a risk factor for arterial dissection because it weakens the vessel walls. Therefore, diagnosis is important to prevent future complications in young patients with recurrent cerebral artery dissection, especially those associated with pregnancy-related morbidities.
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Affiliation(s)
- Hee Sue Kim
- Jeonbuk National University Medical School, Jeonju 54907, Korea;
| | - Eun Su Lee
- Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (E.S.L.); (B.-S.S.)
| | - Byoung-Soo Shin
- Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (E.S.L.); (B.-S.S.)
- Biomedical Research Institute, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea
| | - Hyun Goo Kang
- Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (E.S.L.); (B.-S.S.)
- Biomedical Research Institute, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea
- Correspondence: ; Tel.: +82-63-250-1590
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da Rosa GP, Sousa-Pinto B, Ferreira E, Araújo O, Barilaro G, Bettencourt P, Cervera R, Espinosa G. The presence of non-criteria manifestations negatively affects the prognosis of seronegative antiphospholipid syndrome patients: a multicenter study. Arthritis Res Ther 2022; 24:9. [PMID: 34980238 PMCID: PMC8721999 DOI: 10.1186/s13075-021-02702-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/09/2021] [Indexed: 02/01/2023] Open
Abstract
Background Seronegative antiphospholipid syndrome (SN-APS) is often defined as the presence of APS criteria manifestations, negative antiphospholipid antibodies (aPL), and coexistence of APS non-criteria manifestations. Nevertheless, the impact of these non-criteria features is still unclear. On a different note, the relevance of one single aPL positive determination in patients with APS manifestations is another domain with limited evidence. We aim to compare the course of SN-APS and single-positive aPL (SP-aPL) patients with that of individuals with APS manifestations without non-criteria features/aPL positivity (controls). Methods Retrospective analysis of patients with thrombosis/obstetric morbidity assessed in two European hospitals between 2005 and 2020. Patients were divided into SN-APS, SP-aPL, and control groups. Clinical characteristics, comorbidities, and therapies were compared. Results A total of 82 patients were included in the SN-APS group, 88 in the SP-aPL group, and 185 in the control group. In Cox regression model, SN-APS displayed more thrombosis recurrence than controls (HR 3.8, 95% CI 2.2–6.5, p < 0.001) even when adjusting for the presence of hereditary thrombophilia, systemic lupus erythematosus, or contraceptive hormonal treatment. In SP-aPL, the difference in thrombosis recurrence did not reach statistical significance (p = 0.078). Indefinite anticoagulation (p < 0.001 and p = 0.008, respectively) and vitamin K antagonist (VKA) use (p < 0.001 in both cases) were more common in SN-APS/SP-aPL. Conclusion SN-APS displayed more thrombosis recurrence, indefinite anticoagulation, and VKA use than controls without non-criteria manifestations. The presence of such features in patients with thrombosis and negative aPL may negatively impact their clinical course.
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Affiliation(s)
- Gilberto Pires da Rosa
- Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain.,Faculty of Medicine, University of Porto, Porto, Portugal
| | - Bernardo Sousa-Pinto
- MEDCIDS - Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal.,CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Ester Ferreira
- Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Internal Medicine, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Olga Araújo
- Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain
| | - Giuseppe Barilaro
- Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain
| | - Paulo Bettencourt
- Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Internal Medicine, Hospital CUF, Porto, Portugal
| | - Ricard Cervera
- Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain.
| | - Gerard Espinosa
- Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain
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OUP accepted manuscript. Rheumatology (Oxford) 2022; 61:4187-4197. [DOI: 10.1093/rheumatology/keac045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 12/31/2021] [Indexed: 11/13/2022] Open
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A catastrophic seronegative anti-phospholipid syndrome: case and literature review. Thromb J 2021; 19:103. [PMID: 34930339 PMCID: PMC8685794 DOI: 10.1186/s12959-021-00356-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 12/05/2021] [Indexed: 11/10/2022] Open
Abstract
Background Antiphospholipid Syndrome (APS) is a multisystemic autoimmune disease characterized by arterial and venous thrombosis and / or obstetric morbidity in the presence of at least one circulating anti-phospholipid antibody. The spectrum of vascular events varies from deep venous thrombosis to catastrophic APS, a rare form characterized by acute multiorgan thrombosis and high mortality. Case report We present the case of a 32-week pregnant woman arriving in the hospital emergency room with bilateral acute lower limb ischemia. In the obstetric evaluation, fetal death was declared. Computerized Tomography angiography showed pulmonary embolism of both pulmonary arteries, areas of splenic and right renal infarction and multiple arterial and venous thrombosis. The patient underwent urgent caesarean section and axillary-bifemoral bypass. No events registered. In the postoperative period, in an intensive care unit, treatment with rituximab and plasmapheresis were added to anticoagulant therapy. The laboratorial investigation was negative for thrombophilia and autoimmune diseases. Conclusion Catastrophic APS develops quickly, with multiorgan involvement and high mortality rate. The presented case poses a multidisciplinary challenge, with the surgical approach of extra-anatomical revascularization being less invasive and guaranteeing immediate perfusion of the lower limbs. Although the serological tests were negative for anti-phospholipid antibodies, this case hardly fits into another diagnosis. Therefore, it was treated as a catastrophic APS, having shown a favorable evolution.
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35
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Cohen Tervaert JW, Mohazab N, Redmond D, van Eeden C, Osman M. Breast implant illness: scientific evidence of its existence. Expert Rev Clin Immunol 2021; 18:15-29. [PMID: 34882509 DOI: 10.1080/1744666x.2022.2010546] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
INTRODUCTION More than one million breast augmentation procedures using silicone breast implants (SBI) have been performed worldwide. Adverse events of SBI include local complications such as pain, swelling, redness, infections, capsular contracture, implant rupture and gel-bleed. Furthermore, patients experience systemic symptoms such as chronic fatigue, arthralgias, myalgias, pyrexia, sicca, and cognitive dysfunction. These symptoms received different names such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA) due to silicone incompatibility syndrome and breast implant illness (BII). Because of chronic immune activation, BII/ASIA, allergies, autoimmune diseases, immune deficiencies and finally lymphomas may develop in SBI patients. AREAS COVERED Causality for SBI-related BII/ASIA is reviewed. To address the role of silicone implants in promoting causality, we utilized the Bradford-Hill criteria, with results highlighted in this article. EXPERT OPINION We conclude that there is a causal association between SBIs and BII/ASIA. Using data derived from patients with BII/ASIA and from other medically implanted devices, there appears to be clear pathogenic relationship between SBI and BII/ASIA. Breast implants cause characteristic systemic reactions in certain women, leading to symptoms of sufficient severity to warrant device removal. The morbidity suffered is variable. SBI removal resolves the symptoms in most women and removal is the most effective treatment.
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Affiliation(s)
- J W Cohen Tervaert
- Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - N Mohazab
- Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - D Redmond
- Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - C van Eeden
- Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - M Osman
- Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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Rodríguez CM, Velásquez-Berrío M, Rúa C, Viana M, Abrahams VM, Cadavid AP, Alvarez AM. Antiphospholipid Antibodies From Women With Pregnancy Morbidity and Vascular Thrombosis Induce Endothelial Mitochondrial Dysfunction, mTOR Activation, and Autophagy. Front Physiol 2021; 12:706743. [PMID: 34912234 PMCID: PMC8667788 DOI: 10.3389/fphys.2021.706743] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 10/18/2021] [Indexed: 01/09/2023] Open
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis and pregnancy morbidity (PM) obstetric events together with persistent high titers of circulating antiphospholipid antibodies (aPL). Several mechanisms that explain the development of thrombosis and PM in APS include the association of aPL with alterations in the coagulation cascade and inflammatory events. Other mechanisms disturbing cellular homeostases, such as mitochondrial dysfunction, autophagy, and cell proliferation, have been described in other autoimmune diseases. Therefore, the objective of this study was to investigate the impact of aPL from different patient populations on endothelial cell mitochondrial function, activation of the mammalian target of rapamycin (mTOR) and autophagy pathways, and cellular growth. Using an in vitro model, human umbilical vein endothelial cells (HUVECs) were treated with polyclonal immunoglobulin G (IgG) purified from the serum of women with both PM and vascular thrombosis (PM/VT), with VT only (VT), or with PM and non-criteria aPL (seronegative-obstetric APS, SN-OAPS). We included IgG from women with PM without aPL (PM/aPL-) and healthy women with previous uncomplicated pregnancies (normal human serum, NHS) as control groups. Mitochondrial function, mTOR activation, autophagy, and cell proliferation were evaluated by Western blotting, flow cytometry, and functional assays. IgG from women with PM/VT increased HUVEC mitochondrial hyperpolarization and activation of the mTOR and autophagic pathways, while IgG from patients with VT induced endothelial autophagy and cell proliferation in the absence of elevated mTOR activity or mitochondrial dysfunction. IgG from the SN-OAPS patient group had no effect on any of these HUVEC responses. In conclusion, aPL from women with PM and vascular events induce cellular stress evidenced by mitochondrial hyperpolarization and increased activation of the mTOR and autophagic pathways which may play a role in the pathogenesis of obstetric APS.
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Affiliation(s)
- Carlos M. Rodríguez
- Grupo Reproducción, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia (UdeA), Medellín, Colombia
| | - Manuela Velásquez-Berrío
- Grupo Reproducción, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia (UdeA), Medellín, Colombia
| | - Carolina Rúa
- Grupo de Investigación en Trombosis, Facultad de Medicina, Universidad de Antioquia (UdeA), Medellín, Colombia
| | - Marta Viana
- Grupo de Metabolismo y Función Vascular, Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain
- Red Iberoamericana de Alteraciones Vasculares Asociadas a Transtornos del Embarazo (RIVATREM), Chillán, Chile
| | - Vikki M. Abrahams
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, United States
| | - Angela P. Cadavid
- Grupo Reproducción, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia (UdeA), Medellín, Colombia
- Red Iberoamericana de Alteraciones Vasculares Asociadas a Transtornos del Embarazo (RIVATREM), Chillán, Chile
| | - Angela M. Alvarez
- Grupo Reproducción, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia (UdeA), Medellín, Colombia
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Assan F, Bottin L, Francès C, Moguelet P, Tavolaro S, Barbaud A, de Zuttere D, Alamowitch S, Chasset F. Antiphospholipid-negative Sneddon's syndrome: A comprehensive overview of a rare entity. Ann Dermatol Venereol 2021; 149:3-13. [PMID: 34740467 DOI: 10.1016/j.annder.2021.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 05/26/2021] [Accepted: 08/04/2021] [Indexed: 11/24/2022]
Abstract
The term Sneddon's syndrome (SS) has been used since 1965 to describe a vasculopathy characterized by a combination of cerebrovascular disease with livedo racemosa. SS may be classified as antiphospholipid+ (aPL+) or antiphospholipid- (aPL-). Little is known about aPL- SS; in this review we describe the epidemiology and pathogenesis of aPL- SS, as well as the clinical and histologic features. We discuss recent findings in terms of neurologic and cardiac involvement. Moreover, differential diagnoses of conditions that may present with both livedo racemosa and stroke are discussed. Finally, we discuss real-life practical issues such as the initial investigations to be performed, long-term follow-up, and therapeutic management of aPL- SS patients.
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Affiliation(s)
- F Assan
- Sorbonne University, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, 75020 Paris, France
| | - L Bottin
- Sorbonne University, Faculté de Médecine Sorbonne Université, AP-HP, Service de Neurologie, Hôpital Saint-Antoine, 75012 Paris, France
| | - C Francès
- Sorbonne University, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, 75020 Paris, France
| | - P Moguelet
- Sorbonne University, Faculté de Médecine Sorbonne Université, AP-HP, Service de Pathologie, Hôpital Tenon, 75020 Paris, France
| | - S Tavolaro
- Sorbonne University, Faculté de Médecine Sorbonne Université, AP-HP, Service de Radiologie, Hôpital Tenon, 75020 Paris, France
| | - A Barbaud
- Sorbonne University, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, 75020 Paris, France
| | - D de Zuttere
- Service d'Explorations Fonctionnelles, Hôpital Franco-Britannique, 92300 Levallois-Perret, France
| | - S Alamowitch
- Sorbonne University, Faculté de Médecine Sorbonne Université, AP-HP, Service de Neurologie, Hôpital Saint-Antoine, 75012 Paris, France
| | - F Chasset
- Sorbonne University, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, 75020 Paris, France.
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Hu C, Li S, Xie Z, You H, Jiang H, Shi Y, Qi W, Zhao J, Wang Q, Tian X, Li M, Zhao Y, Zeng X. Evaluation of the Diagnostic Value of Non-criteria Antibodies for Antiphospholipid Syndrome Patients in a Chinese Cohort. Front Immunol 2021; 12:741369. [PMID: 34567005 PMCID: PMC8461188 DOI: 10.3389/fimmu.2021.741369] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 08/20/2021] [Indexed: 11/17/2022] Open
Abstract
Objective Although specific anti-phospholipid antibodies (aPLs) have been used in the diagnosis of the antiphospholipid syndrome (APS) for years, new biomarkers are required to increase its diagnostic and risk-predictive power. This study aimed to explore the value of several non-criteria aPLs in a Chinese cohort. Methods A total of 312 subjects, namely, 100 patients diagnosed with primary APS, 51 with APS secondary to SLE, 71 with SLE, and 90 healthy controls, were recruited. Serum anticardiolipin (aCL) IgG/IgM/IgA, anti-β2-glycoprotein I (aβ2GPI) IgG/IgM/IgA, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, and anti-annexin A5 antibodies (aAnxV) IgG/IgM were tested using ELISA kits. Results Of the total number of patients, 30.46% and 6.62% with APS were positive for aCL or aβ2GPI IgA, respectively, while 39.07% and 24.50% were positive for aAnxV or aPS/PT for at least one antibody (IgG or IgM). The addition test of aCL IgA and aAnxV IgM assists in identifying seronegative APS patients, and IgG aPS/PT was linked to stroke. Conclusion Detection of aCL IgA, aβ2GPI IgA, aAnxV IgG/M, and aPS/PT IgG/M as a biomarker provides additive value in APS diagnosis and would help in risk prediction for APS patients in medical practice.
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Affiliation(s)
- Chaojun Hu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Siting Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Zhijuan Xie
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Hanxiao You
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Hui Jiang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Yu Shi
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Wanting Qi
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Jiuliang Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Qian Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Xinping Tian
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Mengtao Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Yan Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
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Abisror N, Nguyen Y, Marozio L, Esteve Valverde E, Udry S, Pleguezuelo DE, Billoir P, Mayer-Pickel K, Urbanski G, Zigon P, De Moreuil C, Hoxha A, Bezanahary H, Carbillon L, Kayem G, Bornes M, Yelnik C, Johanet C, Nicaise-Roland P, Lambert M, Salle V, Latino OJ, Hachulla E, Benedetto C, Bourrienne MC, Benhamou Y, Alijotas-Reig J, Fain O, Mekinian A. Obstetrical outcome and treatments in seronegative primary APS: data from European retrospective study. RMD Open 2021; 6:0. [PMID: 32848089 PMCID: PMC7507995 DOI: 10.1136/rmdopen-2020-001340] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/27/2020] [Accepted: 07/23/2020] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE To compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical outcome. PATIENTS AND METHODS Inclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease. RESULTS A total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-low-molecular weighted heparin combination. CONCLUSION Several non-criteria APL can be detected in patients with clinical APS features without any conventional APL, with various rates. The detection of non-criteria APL and thus the diagnosis of seronegative APS could discuss the therapeutic management similar to seropositive APS, but well-designed controlled studies are necessary.
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Affiliation(s)
- Noemie Abisror
- Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Paris, France
| | - Yann Nguyen
- Department of Internal Medicine, AP-HP Nord, Beaujon Hospital, Paris University,Clichy, France
| | - Luca Marozio
- Department of Surgical Sciences, Obstetrics and Gynecology, University of Torino, Turin, Italy
| | | | - Sebastian Udry
- 5Autoimmune, Thrombophilic Diseases and Pregnancy Section, Acute Hospital "Dr Carlos G Durand", Buenos Aires, Argentina
| | | | - Paul Billoir
- Department of Internal Medicine, Vascular and Thrombosis Unit, Rouen University Hospital, Normandie University, UNIROUEN, INSERM, Rouen, France
| | | | - Geoffrey Urbanski
- Service Department of internal medicine, CHU d'Angers, Angers, France
| | - Polona Zigon
- Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Claire De Moreuil
- Département de Médecine Vasculaire, Médecine Interne et Pneumologie, CHU de Brest, Hôpital La Cavale Blanche, Brest Cedex, France.,EA 3878, GETBO, Université Bretagne Loire, Brest Cedex, France
| | - Ariela Hoxha
- Department of Medicine-DIMED, Rheumatology Unit, University of Padua, Padua, Italy
| | - Holy Bezanahary
- Department of Internal Medicine, University Hospital of Limoges, Limoges, France
| | - Lionel Carbillon
- Department of Obstetrics, Gynecology and Reproductive Medicine Centers, Hôpitaux Universitaires Paris Seine Saint-Denis, Assistance Publique-Hôpitaux de Paris, Bondy, France.,University of Paris 13, Sorbonne University,Bobigny, France
| | - Gilles Kayem
- Service de Gynécologie Obstétrique, Hôpital Trousseau, AP-HP, Paris, France.,Sorbonne Université,Paris, France
| | - Marie Bornes
- Department of Gynaecology and Obstetrics and Reproductive Medicine, Tenon Hospital, Assistance Publique - Paris Hospitals,Paris, France
| | - Cecile Yelnik
- Service de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest (CeRAINO), Univ. Lille, CHU Lille, Lille, France
| | | | | | - Marc Lambert
- Service de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest (CeRAINO), Univ. Lille, CHU Lille, Lille, France
| | - Valéry Salle
- Department of Internal Medicine, University Hospital of Amiens, Amiens, France
| | - Omar Jose Latino
- 5Autoimmune, Thrombophilic Diseases and Pregnancy Section, Acute Hospital "Dr Carlos G Durand", Buenos Aires, Argentina
| | - Eric Hachulla
- Service de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest (CeRAINO), Univ. Lille, CHU Lille, Lille, France
| | - Chiara Benedetto
- Department of Surgical Sciences, Obstetrics and Gynecology, University of Torino, Turin, Italy
| | - Marie Charlotte Bourrienne
- Université de Paris, INSERM UMR_S1148, Paris cedex 18, France.,Laboratoire d'Hématologie, AP-HP, Hôpital Bichat, Paris cedex 18, France
| | - Ygal Benhamou
- Department of Internal Medicine, Vascular and Thrombosis Unit, Rouen University Hospital, Normandie University, UNIROUEN, INSERM, Rouen, France
| | - Jaume Alijotas-Reig
- Systemic Autoimmune Diseases Unit, Department of Internal Medicine-1, Vall d'Hebron University Hospital, Barcelona, Spain.,Department of Medicine, Faculty of Medicine, Universitat Autönoma de Barcelona, Barcelona, Spain
| | - Olivier Fain
- Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Paris, France
| | - Arsène Mekinian
- Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Paris, France
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Radin M, Barinotti A, Foddai SG, Cecchi I, Rubini E, Roccatello D, Menegatti E, Sciascia S. Cerebrovascular events in patients with isolated anti-phosphatidyl-serine/prothrombin antibodies. Immunol Res 2021; 69:372-377. [PMID: 34245429 PMCID: PMC8342389 DOI: 10.1007/s12026-021-09208-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/15/2021] [Indexed: 11/05/2022]
Abstract
The interest of extra-criteria antiphospholipid antibodies is growing, especially in patients negative for conventional antibodies. In this study we aimed to assess the clinical utility of anti-phosphatidyl-serine/prothrombin antibodies (aPS/PT) testing in patients negative for Beta2-Glycoprotein 1(β2GPI)-dependent tests, for identifying antiphospholipid syndrome (APS) patients that developed cerebrovascular events (CVE). When screening APS patients attending our center, out of 119 aPS/PT IgG/IgM-positive patients, thus patients negative for aβ2GPI and aCL, 42 patients (35%) tested negative for β2GPI-dependent tests and were tested with thrombin generation assay (TGA). Ten patients (24%), with isolated aPS/PT IgG/IgM, had a history of CVE. Lupus anticoagulant (LA)-positive test was more frequently observed in patients with CVE (8/22 vs. 2/20; p = 0.045). Out of the 10 patients who experienced CVE, 3 patients were aPS/PT IgG positive (all LA positive), and 8 patients were aPS/PT IgM positive (6/8 LA positive). One patient was positive for both aPS/PT IgG and IgM. LA-positive patients had only high titers of aPS/PT IgG/IgM, all of them being ≥ 80 U/ml, while the 2 LA-negative patients were aPS/PT IgM positive with medium titers [40-60 U/ml]. LA-positive patients had significantly altered TGA profile when compared to those who were LA negative, considering all TGA parameters. LA-positive patients had significantly higher tLag (8.4 ± 3.3 min vs. 6.6 ± 1.8 min; p = 0.046), higher tPeak (14 ± 4.3 min vs. 11 ± 2.7 min; p = 0.015) and lower Peak (207 ± 152 nM vs. 356.3 ± 104.7 nM; p < 0.001) and lower AUC (2109.7 ± 1006.9 nM vs. 2772.5 ± 776.8 nM; p = 0.033). The use of aPS/PT might be of help in identifying patients with CVE and APS, as also confirmed by TGA testing.
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Affiliation(s)
- Massimo Radin
- Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piedmont and Aosta Valley Network for Rare Diseases, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy.
- School of Specialization of Clinical Pathology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
| | - Alice Barinotti
- Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piedmont and Aosta Valley Network for Rare Diseases, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
- School of Specialization of Clinical Pathology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Silvia Grazietta Foddai
- Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piedmont and Aosta Valley Network for Rare Diseases, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
- School of Specialization of Clinical Pathology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Irene Cecchi
- Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piedmont and Aosta Valley Network for Rare Diseases, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
| | - Elena Rubini
- Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piedmont and Aosta Valley Network for Rare Diseases, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
| | - Dario Roccatello
- Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piedmont and Aosta Valley Network for Rare Diseases, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
- Nephrology and Dialysis, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - Elisa Menegatti
- Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piedmont and Aosta Valley Network for Rare Diseases, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
- School of Specialization of Clinical Pathology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Savino Sciascia
- Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piedmont and Aosta Valley Network for Rare Diseases, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
- Nephrology and Dialysis, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
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Hu C, Li S, Xie Z, You H, Jiang H, Shi Y, Qi W, Zhao J, Wang Q, Tian X, Li M, Zhao Y, Zeng X. Comparison of Different Test Systems for the Detection of Antiphospholipid Antibodies in a Chinese Cohort. Front Immunol 2021; 12:648881. [PMID: 34276646 PMCID: PMC8283786 DOI: 10.3389/fimmu.2021.648881] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 06/17/2021] [Indexed: 11/13/2022] Open
Abstract
Background Diagnosis of antiphospholipid syndrome (APS) is based on the positivity of laboratory criteria antiphospholipid antibodies (aPLs). Test results for aPLs could be contradictory among different detection methods as well as commercial manufacturers. This study aimed to assess and compare the diagnostic and analytic performances of four commercial assays prevalently used in China. Methods A total of 313 patients including 100 patients diagnosed with primary APS, 52 with APS secondary to SLE, 71 with SLE, and 90 health controls were recruited. Serum IgG, IgM, and IgA for aCL, and aβ2GPI antibodies were detected with two ELISA and two CLIA systems, and test system with the best diagnostic value was explored of its correlation with key clinical features. Results CLIA by YHLO Biotech Co. was considered as the system with the best predictive power, where 58.55 and 57.89% of APS patients were positive for aCL or aβ2GPI for at least one antibody (IgG or IgM or IgA). Overall, CLIA showed better performance characteristics than traditional ELISA test systems. Conclusion CLIA was considered as a better platform for aPL detection in APS diagnosis. A combination of other detection platforms could assist in differential diagnosis as well as in identifying high-risk patients.
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Affiliation(s)
- Chaojun Hu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Siting Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Zhijuan Xie
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Hanxiao You
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Hui Jiang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Yu Shi
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Wanting Qi
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Jiuliang Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Qian Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Xinping Tian
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Mengtao Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Yan Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
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Truglia S, Mancuso S, Capozzi A, Recalchi S, Riitano G, Longo A, De Carolis S, Spinelli FR, Alessandri C, Ceccarelli F, De Carolis C, Misasi R, Sorice M, Conti F. "Non-criteria antiphospholipid antibodies": bridging the gap between seropositive and seronegative Antiphospholipid Syndrome. Rheumatology (Oxford) 2021; 61:826-833. [PMID: 33970223 DOI: 10.1093/rheumatology/keab414] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 05/03/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE We aimed to analyze the prevalence of non-criteria anti-phospholipid (aPL) antibodies and their role in the diagnosis, treatment and prognosis in a cohort of patients with clinical features consistent with a diagnosis of antiphospholipid syndrome (APS), but persistently negative for criteria aPL-anti-cardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2-GPI), and lupus anticoagulant (LA) - named seronegative APS (SN-APS). METHODS Sera from SN-APS patients were tested for aCL by TLC-immunostaining, anti-vimentin/cardiolipin (aVim/CL) and anti-phosphatidylserine/prothrombin (anti-PS/PT) by ELISA. Control groups of our study were APS patients and healthy controls. RESULTS We enrolled 114 consecutive SN-APS patients, 69 (60.5%) resulted positive for at least one non-criteria test in two occasions 12 weeks apart. Among the persistently positive patients to these tests, 97% resulted positive for aCL by TLC-immunostaining, 52.3% for aVim/CL and 17.4% for aPS/PT. SN-APS patients with double positivity (aCL by TLC-immunostaining and aVim/CL) showed a likelihood positive ratio of 8 to present mixed thrombotic and obstetrical features. Among SN-APS patients tested positive, after the therapeutic changes, 3 cases of recurrent thrombosis were observed [median follow-up 41 months (IQR 39.5)]. Twenty pregnancies were recorded in 17 SN-APS patients after the detection of unconventional aPL and 12 of them (60%) experienced a good outcome under conventional treatment for APS. CONCLUSIONS This is the largest monocentric study demonstrating that aCL tested by TLC-immunostaining and aVim/CL can detect aPL positivity in SN-APS. It may encourage clinicians to monitoring and providing adequate targeted therapy, which improve SN-APS prognosis.
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Affiliation(s)
- Simona Truglia
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università Roma, Rome, Italy
| | - Silvia Mancuso
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università Roma, Rome, Italy
| | - Antonella Capozzi
- Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy
| | - Serena Recalchi
- Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy
| | - Gloria Riitano
- Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy
| | - Agostina Longo
- Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy
| | - Sara De Carolis
- Department of Obstetrics, Gynaecology and Pediatrics, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Francesca Romana Spinelli
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università Roma, Rome, Italy
| | - Cristiano Alessandri
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università Roma, Rome, Italy
| | - Fulvia Ceccarelli
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università Roma, Rome, Italy
| | - Caterina De Carolis
- UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy
| | - Roberta Misasi
- Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy
| | - Maurizio Sorice
- Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy
| | - Fabrizio Conti
- Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università Roma, Rome, Italy
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Dieudonné Y, Guffroy A, Poindron V, Sprauel PS, Martin T, Korganow AS, Gies V. B cells in primary antiphospholipid syndrome: Review and remaining challenges. Autoimmun Rev 2021; 20:102798. [PMID: 33722752 DOI: 10.1016/j.autrev.2021.102798] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 01/03/2021] [Indexed: 02/03/2023]
Abstract
It is now widely accepted that antiphospholipid antibodies (aPL) have direct pathogenic effects and that B cells, notably through aPL production, play a key role in the development of antiphospholipid syndrome (APS). Recent findings strengthened the implication of B cells with the description of specific B cell phenotype abnormalities and inborn errors of immunity involving B cell signaling in APS patients. In addition, it has been shown in preclinical models that cross-reactivity between APS autoantigens and mimotopes expressed by human gut commensals can lead to B cell tolerance breakdown and are sufficient for APS development. However, B cell targeting therapies are surprisingly not as effective as expected in APS compared to other autoimmune diseases. Elucidation of the B cell tolerance breakdown mechanisms in APS patients may help to develop and guide the use of novel therapeutic agents that target B cells or specific immune pathway.
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Affiliation(s)
- Yannick Dieudonné
- Université de Strasbourg, INSERM UMR - S1109, F-67000 Strasbourg, France; Hôpitaux Universitaires de Strasbourg, Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiencies, F-67000 Strasbourg, France; Université de Strasbourg, Faculty of Medicine, F-67000 Strasbourg, France.
| | - Aurélien Guffroy
- Université de Strasbourg, INSERM UMR - S1109, F-67000 Strasbourg, France; Hôpitaux Universitaires de Strasbourg, Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiencies, F-67000 Strasbourg, France; Université de Strasbourg, Faculty of Medicine, F-67000 Strasbourg, France
| | - Vincent Poindron
- Université de Strasbourg, INSERM UMR - S1109, F-67000 Strasbourg, France; Hôpitaux Universitaires de Strasbourg, Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiencies, F-67000 Strasbourg, France; Université de Strasbourg, Faculty of Medicine, F-67000 Strasbourg, France
| | - Pauline Soulas Sprauel
- Université de Strasbourg, INSERM UMR - S1109, F-67000 Strasbourg, France; Hôpitaux Universitaires de Strasbourg, Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiencies, F-67000 Strasbourg, France; Université de Strasbourg, Faculty of Pharmacy, F-67400 Illkirch, France
| | - Thierry Martin
- Université de Strasbourg, INSERM UMR - S1109, F-67000 Strasbourg, France; Hôpitaux Universitaires de Strasbourg, Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiencies, F-67000 Strasbourg, France; Université de Strasbourg, Faculty of Medicine, F-67000 Strasbourg, France
| | - Anne-Sophie Korganow
- Université de Strasbourg, INSERM UMR - S1109, F-67000 Strasbourg, France; Hôpitaux Universitaires de Strasbourg, Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiencies, F-67000 Strasbourg, France; Université de Strasbourg, Faculty of Medicine, F-67000 Strasbourg, France
| | - Vincent Gies
- Université de Strasbourg, INSERM UMR - S1109, F-67000 Strasbourg, France; Hôpitaux Universitaires de Strasbourg, Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiencies, F-67000 Strasbourg, France; Université de Strasbourg, Faculty of Pharmacy, F-67400 Illkirch, France
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Radin M, Cecchi I, Foddai SG, Rubini E, Barinotti A, Ramirez C, Seaman A, Roccatello D, Mahler M, Sciascia S. Validation of the Particle-Based Multi-Analyte Technology for Detection of Anti-PhosphatidylSerine/Prothrombin Antibodies. Biomedicines 2020; 8:biomedicines8120622. [PMID: 33348782 PMCID: PMC7766094 DOI: 10.3390/biomedicines8120622] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 11/16/2022] Open
Abstract
Among “extra-criteria” antiphospholipid (aPL) antibodies, anti-phosphatidylserine/prothrombin (aPS/PT) antibodies, are considered a part of risk assessment strategies when investigating patients suspected of having antiphospholipid syndrome (APS). aPL detection is currently performed by solid-phase assays to identify anti-cardiolipin (aCL), anti-β2glycoprotein I (aβ2GPI) and aPS/PT antibodies, but new techniques are emerging. Among these, particle-based multi-analyte technology (PMAT), which allows the full automation and simultaneous digital detection of autoantibodies and proteins, including IgG, IgA and IgM isotypes of aCL, aβ2GPI and aPS/PT. The aim of this study was to investigate the agreement of aPS/PT testing between enzyme-linked immunosorbent assay (ELISA) and the PMAT platform. A total of 94 patients were enrolled in the study, including 71 patients with confirmed APS and 23 “aPL carriers”. aPS/PT IgG showed a moderate binomial agreement between ELISA and PMAT (k = 0.57, 95% CI 0.45–0.75), and aPS/PT IgM showed a moderate agreement (k = 0.60, 95% CI 0.45–0.75). Moreover, when considering the continuous agreement, both aPS/PT IgG and IgM showed a statistically significant correlation between ELISA and PMAT (Spearman’s correlation = 0.69, p < 0.001 and 0.72, p < 0.001, respectively). This study demonstrates that PMAT technology is a reliable method for aPS/PT IgG and IgM testing when compared to the available commercial ELISA kit.
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Affiliation(s)
- Massimo Radin
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
| | - Irene Cecchi
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
| | - Silvia Grazietta Foddai
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
- School of Specialization of Clinical Pathology, Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy
| | - Elena Rubini
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
| | - Alice Barinotti
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
| | - Carlos Ramirez
- Inova Diagnostics, San Diego, CA 92131, USA; (C.R.); (A.S.); (M.M.)
| | - Andrea Seaman
- Inova Diagnostics, San Diego, CA 92131, USA; (C.R.); (A.S.); (M.M.)
| | - Dario Roccatello
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
- Nephrology and Dialysis, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, 10154 Turin, Italy
| | - Michael Mahler
- Inova Diagnostics, San Diego, CA 92131, USA; (C.R.); (A.S.); (M.M.)
| | - Savino Sciascia
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
- Nephrology and Dialysis, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, 10154 Turin, Italy
- Correspondence: mail
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The Weight of IgA Anti-β2glycoprotein I in the Antiphospholipid Syndrome Pathogenesis: Closing the Gap of Seronegative Antiphospholipid Syndrome. Int J Mol Sci 2020; 21:ijms21238972. [PMID: 33255963 PMCID: PMC7730063 DOI: 10.3390/ijms21238972] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/20/2020] [Accepted: 11/23/2020] [Indexed: 12/12/2022] Open
Abstract
The specific value of IgA Anti-β2glycoprotein I antibodies (aB2GP1) in the diagnosis and management of antiphospholipid syndrome (APS) is still controversial and a matter of active debate. The relevance of the IgA aB2GP1 isotype in the pathophysiology of APS has been increasingly studied in the last years. There is well know that subjects with multiple positive APS tests are at increased risk of thrombosis and/or miscarriage. However, these antibodies are not included in the 2006 APS classification criteria. Since 2010 the task force of the Galveston International Congress on APS recommends testing IgA aB2GP1 isotype in patients with APS clinical criteria in the absence of criteria antibodies. In this review, we summarize the molecular and clinical “state of the art” of the IgA aB2GP in the context of APS. We also discuss some of the characteristics that may help to evaluate the real value of the IgA aB2GP1 determination in basic research and clinical practice. The scientific community should be aware of the importance of clarifying the role of IgA aB2GP1 in the APS diagnosis.
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Zuo Y, Estes SK, Ali RA, Gandhi AA, Yalavarthi S, Shi H, Sule G, Gockman K, Madison JA, Zuo M, Yadav V, Wang J, Woodard W, Lezak SP, Lugogo NL, Smith SA, Morrissey JH, Kanthi Y, Knight JS. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med 2020; 12:eabd3876. [PMID: 33139519 PMCID: PMC7724273 DOI: 10.1126/scitranslmed.abd3876] [Citation(s) in RCA: 439] [Impact Index Per Article: 87.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 09/14/2020] [Accepted: 10/30/2020] [Indexed: 01/08/2023]
Abstract
Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions. Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease. Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies). Case series have recently detected aPL antibodies in patients with COVID-19. Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19. These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti-β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM. We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples. Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer's threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units). Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate. Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals. Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models. These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.
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Affiliation(s)
- Yu Zuo
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Shanea K Estes
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Ramadan A Ali
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Alex A Gandhi
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Srilakshmi Yalavarthi
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Hui Shi
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
- Division of Rheumatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gautam Sule
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Kelsey Gockman
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Jacqueline A Madison
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Melanie Zuo
- Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Vinita Yadav
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Jintao Wang
- Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA
| | - Wrenn Woodard
- Michigan Clinical Research Unit, University of Michigan, Ann Arbor, MI 48109, USA
| | - Sean P Lezak
- Michigan Clinical Research Unit, University of Michigan, Ann Arbor, MI 48109, USA
| | - Njira L Lugogo
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Stephanie A Smith
- Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
| | - James H Morrissey
- Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
| | - Yogendra Kanthi
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
- Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA
| | - Jason S Knight
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
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Management of Antiphospholipid Syndrome. Biomedicines 2020; 8:biomedicines8110508. [PMID: 33212808 PMCID: PMC7696303 DOI: 10.3390/biomedicines8110508] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/09/2020] [Accepted: 11/14/2020] [Indexed: 02/07/2023] Open
Abstract
Antiphospholipid syndrome (APS), is an acquired autoimmune disorder characterised by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL). Although venous thromboembolism is the most common manifestation, thrombotic events in APS may also occur in virtually any vascular bed, with cerebral circulation being the arterial territory most commonly affected. As APS is a heterogeneous condition, its management should be tailored with a patient-centred approach based on individual risk assessment, which includes the aPL profile, concomitant auto-immune diseases, and traditional cardiovascular risk factors. Although literature data are conflicting regarding primary prophylaxis, there is some evidence indicating that antiplatelet agents may reduce the risk of a first thrombotic event in individuals with a high-risk profile. In patients with thrombotic APS, current evidence-based guidelines recommend lifelong vitamin K antagonists (VKAs), preferably warfarin. The optimal intensity of anticoagulation following arterial thrombosis remains controversial. Arterial thrombosis should be treated either with high-intensity warfarin at a target INR > 3.0, or low-dose aspirin (LDA) combined with moderate-intensity warfarin (INR 2.0-3.0). It is recommended to avoid direct oral anticoagulants (DOACs) in patients with high-risk APS, mainly those with triple-positive PL and previous arterial events. They would only be used exceptionally in selected patients with low-risk venous thromboembolism (VTE). In low-risk VTE patients currently treated with a DOAC due to warfarin intolerance or a previous unstable International Normalized Ratio on warfarin, the decision of continuing DOACs would be taken in carefully selected patients. In women with obstetric APS, the combination therapy with LDA plus heparin remains the conventional strategy.
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Misasi R, Longo A, Recalchi S, Caissutti D, Riitano G, Manganelli V, Garofalo T, Sorice M, Capozzi A. Molecular Mechanisms of "Antiphospholipid Antibodies" and Their Paradoxical Role in the Pathogenesis of "Seronegative APS". Int J Mol Sci 2020; 21:ijms21218411. [PMID: 33182499 PMCID: PMC7665122 DOI: 10.3390/ijms21218411] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 10/30/2020] [Accepted: 11/06/2020] [Indexed: 02/06/2023] Open
Abstract
Antiphospholipid Syndrome (APS) is an autoimmune disease characterized by arterial and/or venous thrombosis and/or pregnancy morbidity, associated with circulating antiphospholipid antibodies (aPL). In some cases, patients with a clinical profile indicative of APS (thrombosis, recurrent miscarriages or fetal loss), who are persistently negative for conventional laboratory diagnostic criteria, are classified as "seronegative" APS patients (SN-APS). Several findings suggest that aPL, which target phospholipids and/or phospholipid binding proteins, mainly β-glycoprotein I (β-GPI), may contribute to thrombotic diathesis by interfering with hemostasis. Despite the strong association between aPL and thrombosis, the exact pathogenic mechanisms underlying thrombotic events and pregnancy morbidity in APS have not yet been fully elucidated and multiple mechanisms may be involved. Furthermore, in many SN-APS patients, it is possible to demonstrate the presence of unconventional aPL ("non-criteria" aPL) or to detect aPL with alternative laboratory methods. These findings allowed the scientists to study the pathogenic mechanism of SN-APS. This review is focused on the evidence showing that these antibodies may play a functional role in the signal transduction pathway(s) leading to thrombosis and pregnancy morbidity in SN-APS. A better comprehension of the molecular mechanisms triggered by aPL may drive development of potential therapeutic strategies in APS patients.
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Pires da Rosa G, Bettencourt P, Rodríguez-Pintó I, Cervera R, Espinosa G. "Non-criteria" antiphospholipid syndrome: A nomenclature proposal. Autoimmun Rev 2020; 19:102689. [PMID: 33223008 DOI: 10.1016/j.autrev.2020.102689] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 06/02/2020] [Indexed: 12/12/2022]
Abstract
The classification criteria for antiphospholipid syndrome (APS) generate discussion, with a growing impression that certain patients not fulfilling these criteria might be inadequately excluded from the classification. Nonetheless, these "non-criteria" patients are heterogeneously defined across different publications. We reviewed the "non-criteria" APS subgroups depicted in the literature and attempted to organize these subsets in a nomenclature proposal that could be used for research purposes. We established four potential patient profiles, grouped under the broad term "non-criteria APS": (A) "Seronegative APS": patients fulfilling clinical criteria, plus "non-criteria" manifestations, with persistently negative antiphospholipid antibodies (aPL); (B) "Clinical non-criteria APS": patients with "non-criteria" manifestations, plus aPL positivity fulfilling the classification criteria; (C) "Incomplete laboratory APS": patients fulfilling clinical criteria, plus positive aPL, but not fulfilling the classification criteria (low titer aPL); and (D) "Laboratory non-criteria APS": patients fulfilling clinical criteria, with negative or low titer criteria aPL, plus positive "non-criteria" aPL. This categorization could allow for a more homogeneous research approach to APS, enabling more sustained and universal conclusions.
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Affiliation(s)
- Gilberto Pires da Rosa
- Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain; Faculty of Medicine, University of Porto, Porto, Portugal
| | - Paulo Bettencourt
- Faculty of Medicine, University of Porto, Porto, Portugal; Internal Medicine Department, Hospital CUF, Porto, Portugal
| | - Ignasi Rodríguez-Pintó
- Autoimmune Diseases Unit, Hospital Universitari Mútua de Terrassa, Terrassa, Catalonia, Spain
| | - Ricard Cervera
- Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain
| | - Gerard Espinosa
- Department of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain.
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50
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Hu C, Li X, Zhao J, Wang Q, Li M, Tian X, Zeng X. Immunoglobulin A Isotype of Antiphospholipid Antibodies Does Not Provide Added Value for the Diagnosis of Antiphospholipid Syndrome in a Chinese Population. Front Immunol 2020; 11:568503. [PMID: 33123140 PMCID: PMC7573363 DOI: 10.3389/fimmu.2020.568503] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 09/14/2020] [Indexed: 12/23/2022] Open
Abstract
Objective Antiphospholipid syndrome (APS) is characterized by the presence of anti-phospholipid (aPL) antibodies. However, the relationship between the immunoglobulin (Ig) A isotype of aPL positivity and its clinical utility in APS diagnosis is controversial. Presently, we determine the clinical utility of IgA-aPL from consecutive patients in a large cohort from the Chinese population and patients with APS whose aPL profiles were obtained. Methods The detection of anticardiolipin (aCL) and anti-β2 glycoprotein-Ⅰ (aβ2GPⅠ) antibodies of the IgA/IgG/IgM isotype by paramagnetic particle chemiluminescent immunoassay was carried out in sera from 7293 subjects. 153 primary APS (PAPS) patients and 59 patients with secondary APS (SAPS) were included in this study. Results In total, 1,082 out of 7,293 (2.55%) subjects had a positive IgA-aPL test, and the prevalence of isolated IgA-aPL was 0.29% (21/7,293) in the general population. The prevalence of IgA-aPL in the PAPS patients was 12.42% (19/153); however, only one patient (0.65%) presented with isolated IgA-aPL. Fifty (25.9%) of the SAPS had IgA-aPL, none of whom lacked IgG/IgM-aPL. The combination of the IgA isotype and the IgG/IgM isotype did not increase the diagnostic performance when compared with the IgG/IgM isotype of aCL or aβ2GPⅠ, respectively. IgA-aPL was not associated with clinical manifestation in patients with APS. Conclusion Isolated IgA-aPL is rare in the general population as well as in patients with APS. Whether in the laboratory or in clinical practice, the presence of IgA-aPL does not provide added value for the diagnosis of APS in the Chinese population.
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Affiliation(s)
- Chaojun Hu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Xi Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jiuliang Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Qian Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Mengtao Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Xinping Tian
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
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