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Ullah A, Ding X, Qi* X, Liu* H. The Discovery of New Antibody in Autoimmune Disease Using a Novel Approach of Coombs Test Based on Flow Cytometry Method. J Clin Lab Anal 2025; 39:e25148. [PMID: 39829383 PMCID: PMC11821728 DOI: 10.1002/jcla.25148] [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: 03/08/2024] [Revised: 12/09/2024] [Accepted: 12/22/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND AND OBJECTIVE The objective of this study was to investigate the antibody to RBC in autoimmune disease patients with ANA using sensitive Coombs test based on flow cytometry method. MATERIALS AND METHODS Antinuclear antibodies (ANA) of autoimmune disease patients were added to red blood cells (RBCs) of blood group O. At the same time, healthy individuals' serums were also checked. The sample tubes were incubated for 30 min at 37°C. After incubation, each sample was analyzed on flow cytometry. RESULTS The agglutination of antinuclear antibodies in autoimmune patients was observed, while in healthy people, there was no agglutination between RBCs and serum. A significant difference was found between the disease group and healthy group (p < 0.0001) showing that a statistical analysis was conducted to compare the presence of ANA agglutination between the two groups. The reported p-value of less than 0.0001 shows that the observed difference is highly significant. The serum stability test conducted over ten consecutive days demonstrated a CV of 6.90% in the test results, indicating favorable stability. CONCLUSION In conclusion, this study emphasizes the effectiveness of flow cytometry as a valuable tool for detecting RBC-bound antibodies and new antibodies in autoimmune disease patients. Its high sensitivity and accuracy have the potential to greatly improve diagnostic capabilities in clinical laboratories.
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Affiliation(s)
- Anwar Ullah
- College of Medical LaboratoryDalian Medical UniversityDalianChina
| | - Xuewei Ding
- College of Medical LaboratoryDalian Medical UniversityDalianChina
| | - Xia Qi*
- College of Medical LaboratoryDalian Medical UniversityDalianChina
| | - Hui Liu*
- College of Medical LaboratoryDalian Medical UniversityDalianChina
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Shani U, David P, Balassiano Strosberg I, Regev O, Yihia M, Ben-Shabat N, McGonagle D, Weinstein O, Amital H, Watad A. Mortality in Antinuclear Antibody-Positive Patients with and Without Rheumatologic Immune-Related Disorders: A Large-Scale Population-Based Study. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:60. [PMID: 39859043 PMCID: PMC11767202 DOI: 10.3390/medicina61010060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 12/24/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025]
Abstract
Background & Objectives: To explore the potential association between positive ANA serology and all-cause mortality in a large cohort of patients, including those with and without rheumatological conditions and other immune-related diseases. Material and Methods: A retrospective cohort study analyzed all-cause mortality among 205,862 patients from Clalit Health Services (CHS), Israel's largest health maintenance organization (HMO). We compared patients aged 18 and older with positive ANA serology (n = 102,931) to an equal number of ANA-negative controls (n = 102,931). Multivariable Cox regression models were used to assess hazard ratios (HR) for mortality, adjusting for demographic and clinical factors. Results: ANA positivity was strongly associated with increased mortality (adjusted HR [aHR] 4.62; 95% CI 4.5-4.7, p < 0.001). Significant predictors of mortality included male gender (39.2% vs. 24.4%, p < 0.001), older age at testing (72.4 ± 13.0 vs. 50.1 ± 17.3 years, p < 0.001), and Jewish ethnicity (89.6% vs. 83.2%, p < 0.001). Certain ANA patterns, such as mitochondrial (and dense fine speckled (DFS-AC2)), were highly predictive of mortality, with aHRs of 36.14 (95% CI 29.78-43.85) and 29.77 (95% CI 26.58-33.34), respectively. ANA-positive patients with comorbid rheumatological immune-related disorders (RIRDs) demonstrated a higher survival rate compared to those without such a condition (aHR 0.9, 95% CI 0.86-0.95, p < 0.001). This finding remained significant after adjusting for several parameters, including age. Conclusions: ANA positivity is associated with increased all-cause mortality, particularly in individuals without rheumatologic disorders, after adjusting for confounders such as age. This may indicate occult malignancies, cardiovascular pathology, or chronic inflammatory states, necessitating more vigilant surveillance.
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Affiliation(s)
- Uria Shani
- Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel; (U.S.); (P.D.); (I.B.S.); (N.B.-S.); (H.A.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel; (O.R.); (M.Y.)
| | - Paula David
- Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel; (U.S.); (P.D.); (I.B.S.); (N.B.-S.); (H.A.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel; (O.R.); (M.Y.)
- Section of Musculoskeletal Disease, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Chapel Allerton Hospital, Leeds LS7 4SA, UK;
| | - Ilana Balassiano Strosberg
- Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel; (U.S.); (P.D.); (I.B.S.); (N.B.-S.); (H.A.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel; (O.R.); (M.Y.)
| | - Ohad Regev
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel; (O.R.); (M.Y.)
| | - Mohamad Yihia
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel; (O.R.); (M.Y.)
- Department of Geriatrics, Sheba Medical Center, Tel-Hashomer 5262100, Israel
| | - Niv Ben-Shabat
- Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel; (U.S.); (P.D.); (I.B.S.); (N.B.-S.); (H.A.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel; (O.R.); (M.Y.)
| | - Dennis McGonagle
- Section of Musculoskeletal Disease, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Chapel Allerton Hospital, Leeds LS7 4SA, UK;
| | - Orly Weinstein
- Clalit Health Services, Tel-Aviv 4933355, Israel;
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Ben-Gurion Ave., Beer Sheva 8410501, Israel
| | - Howard Amital
- Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel; (U.S.); (P.D.); (I.B.S.); (N.B.-S.); (H.A.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel; (O.R.); (M.Y.)
| | - Abdulla Watad
- Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel; (U.S.); (P.D.); (I.B.S.); (N.B.-S.); (H.A.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel; (O.R.); (M.Y.)
- Section of Musculoskeletal Disease, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Chapel Allerton Hospital, Leeds LS7 4SA, UK;
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Kraev K, Hristov B, Uchikov P, Kraeva M, Basheva-Kraeva Y, Valova S, Koleva-Ivanova M, Popova-Belova S, Sandeva M, Chakarov D, Geneva-Popova M. Comprehensive Exploration of Antinuclear Antibodies (ANAs): Unveiling Clinical Significance, Associations with Cancer, and the Nuances of Differential Diagnosis in Positive ANA Patients. Diagnostics (Basel) 2024; 14:320. [PMID: 38337836 PMCID: PMC10855796 DOI: 10.3390/diagnostics14030320] [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: 01/15/2024] [Revised: 01/31/2024] [Accepted: 01/31/2024] [Indexed: 02/12/2024] Open
Abstract
This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs' diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions.
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Affiliation(s)
- Krasimir Kraev
- Department of Propaedeutics of Internal Diseases “Prof. Dr. Anton Mitov”, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria; (S.P.-B.); (M.G.-P.)
| | - Bozhidar Hristov
- Second Department of Internal Diseases, Section “Gastroenterology”, Medical Faculty, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria;
| | - Petar Uchikov
- Department of Special Surgery, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria;
| | - Maria Kraeva
- Department of Otorhinolaryngology, Medical Faculty, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria;
| | - Yordanka Basheva-Kraeva
- Department of Ophthalmology, Medical Faculty, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria
| | - Siyana Valova
- Second Department of Internal Diseases, Section “Nephrology”, Medical Faculty, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria;
| | - Maria Koleva-Ivanova
- Department of General and Clinical Pathology, Faculty of Medicine, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria;
| | - Stanislava Popova-Belova
- Department of Propaedeutics of Internal Diseases “Prof. Dr. Anton Mitov”, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria; (S.P.-B.); (M.G.-P.)
| | - Milena Sandeva
- Department of Midwifery, Faculty of Public Health, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria;
| | - Dzhevdet Chakarov
- Department of Propaedeutics of Surgical Diseases, Section of General Surgery, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria
| | - Mariela Geneva-Popova
- Department of Propaedeutics of Internal Diseases “Prof. Dr. Anton Mitov”, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria; (S.P.-B.); (M.G.-P.)
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Xiang HY, Xiang XY, Ten TB, Ding X, Liu YW, Luo CH. Clinical value of chemiluminescence method for detection of antinuclear antibody profiles. World J Clin Cases 2023; 11:6688-6697. [PMID: 37901001 PMCID: PMC10600859 DOI: 10.12998/wjcc.v11.i28.6688] [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: 07/06/2023] [Revised: 07/28/2023] [Accepted: 08/31/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND Antinuclear antibodies (ANAs) are crucial in diagnosing autoimmune diseases, mainly systemic lupus erythematosus (SLE). This study aimed to compare the performance of chemiluminescence assay (CLIA) and line immunoassay (LIA) in detecting ANAs in patients with autoimmune diseases, evaluate their diagnostic accuracy for SLE, and develop a novel diagnostic model using CLIA-detected antibodies for SLE. Specimens from patients with autoimmune diseases and physical examination specimens were collected to parallel detect specific antibodies. Individual antibodies' diagnostic performance and a model combining multiple antibodies were assessed. The findings provide valuable insights into improving the diagnosis of SLE through innovative approaches. AIM To compare the performance of CLIA and LIA in detecting ANAs in patients with autoimmune diseases, assess their accuracy for SLE, and develop a novel diagnostic model using CLIA-detected antibodies for SLE. METHODS Specimens have been obtained from 270 patients with clinically diagnosed autoimmune disorders, as well as 130 physical examination specimens. After that, parallel detection of anti-double-stranded DNA (dsDNA) antibody, anti-histone (Histone) antibody, anti-nucleosome (Nuc) antibody, anti-Smith (Sm) antibody, anti-ribosomal P protein (Rib-P) antibody, anti-sicca syndrome A (Ro60) antibody, anti-sicca syndrome A (Ro52) antibody, anti-sicca syndrome (SSB) antibody, anti-centromere protein B (Cenp-B) antibody, anti-DNA topoisomerase 1 (Scl-70) antibody, anti-histidyl tRNA synthetase (Jo-1) antibody, and anti-mitochondrial M2 (AMA-M2) antibody was performed using CLIA and LIA. The detection rates, compliance rates, and diagnostic performance for SLE were compared between the two methodologies, followed by developing a novel diagnostic model for SLE. RESULTS CLIA and LIA exhibited essentially comparable detection rates for anti-dsDNA antibody, anti-Histone antibody, anti-Nuc antibody, anti-Sm antibody, anti-Rib-P antibody, anti-Ro60 antibody, anti-Ro52 antibody, anti-SSB antibody, anti-Cenp-B antibody, anti-DNAScl-70 antibody, anti-Jo-1 antibody and anti-AMA-M2 antibody (P > 0.05). The two methods displayed identical results for the detection of anti-dsDNA antibody, anti-Histone antibody, anti-Nuc antibody, anti-Sm antibody, anti-Ro60 antibody, anti-Ro52 antibody, anti-SSB antibody, anti-Cenp-B antibody, anti-Scl-70 antibody, and anti-AMA-M2 antibody (Kappa > 0.7, P < 0.05), but showed a moderate agreement for the detection of anti-Rib-P antibody and anti-Jo-1 antibody (Kappa = 0.671 and 0.665; P < 0.05). In addition, the diagnostic performance of these antibodies detected by both methods was similar for SLE. The diagnostic model's area under the curve values, sensitivity, and specificity, including an anti-dsDNA antibody and an anti-Ro60 antibody detected by CLIA, were 0.997, 0.962, and 0.978, respectively. These values were higher than the diagnostic performance of individual antibodies. CONCLUSION CLIA and LIA demonstrated excellent overall consistency in detecting ANA profiles. A diagnostic model based on CLIA-detected antibodies can successfully contribute to developing a novel technique for detecting SLE.
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Affiliation(s)
- Hui-Yao Xiang
- Medical Laboratory Science, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443003, Hubei Province, China
| | - Xi-Ying Xiang
- Medical Laboratory Science, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443003, Hubei Province, China
| | - Ting-Bo Ten
- Medical Laboratory Science, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443003, Hubei Province, China
| | - Xie Ding
- Medical Laboratory Science, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443003, Hubei Province, China
| | - Yu-Wen Liu
- Medical Laboratory Science, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443003, Hubei Province, China
| | - Chun-Hua Luo
- Medical Laboratory Science, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443003, Hubei Province, China
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Park MJ, Jang HM, Kim D, Won DI, Baek HS, Cho MH. Differences in the Clinical Significance of Antinuclear Antibodies According to Titers and Patterns in Children. Clin Pediatr (Phila) 2023; 62:1254-1260. [PMID: 36829288 DOI: 10.1177/00099228231154948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/26/2023]
Abstract
This study aimed to evaluate the differences in the clinical significance of antinuclear antibody (ANA) according to their titers and patterns in the diagnosis of systemic autoimmune diseases (AiD) in pediatric patients. Of the 2442 children who had undergone an ANA test, 473 (19.4%) were positive for ANA, of whom 33 (7.0%) were diagnosed with significant AiD. The positive predictive value (PPV) for significant AiD was considerably high on application of an ANA titer of ≥1:640, and the PPV of a dense fine speckled (DFS) pattern was significantly lower compared with those of speckled and homogenous patterns. The diagnostic value of ANA positivity for AiD is limited, and the clinical significance of the DFS pattern is relatively lower compared with that of other patterns, such as homogenous and speckled patterns, in children. It is necessary to approach the significance of ANA in children individually depending on titers and patterns.
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Affiliation(s)
- Min Ji Park
- Department of Pediatrics, Kyungpook National University, School of Medicine, Daegu, Republic of Korea
| | - Hae Min Jang
- Department of Pediatrics, Kyungpook National University, School of Medicine, Daegu, Republic of Korea
| | - Dongsub Kim
- Department of Pediatrics, Kyungpook National University, School of Medicine, Daegu, Republic of Korea
| | - Dong Il Won
- Department of Clinical Pathology, Kyungpook National University, School of Medicine, Daegu, Republic of Korea
| | - Hee Sun Baek
- Department of Pediatrics, Yeungnam University, College of Medicine, Daegu, Republic of Korea
| | - Min Hyun Cho
- Department of Pediatrics, Kyungpook National University, School of Medicine, Daegu, Republic of Korea
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Weltzsch JP, Ziegler A, Lohse A. [Autoimmune hepatitis : From autoantibodies to cirrhosis]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2023:10.1007/s00108-023-01519-9. [PMID: 37306752 DOI: 10.1007/s00108-023-01519-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Accepted: 04/12/2023] [Indexed: 06/13/2023]
Abstract
Autoimmune Hepatitis (AIH) is an immune-mediated liver disease of unknown origin. Its clinical presentation is heterogeneous and ranges from asymptomatic courses over several years to acute forms with acute liver failure. Accordingly, the diagnosis is only made at the stage of cirrhosis in about one third of affected individuals. Early diagnosis and a consistent, adequate, individualized, immunosuppressive therapy are crucial for the prognosis, which is excellent when treated properly. AIH is rare in the general population and can be easily overlooked due to its variable clinical picture and sometimes difficult diagnosis. AIH should be considered as a differential diagnosis in any unclear acute or chronic hepatopathy. The therapy initially consists of remission induction and subsequently maintenance therapy with (often lifelong) immunosuppressants.
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Affiliation(s)
- Jan Philipp Weltzsch
- I. Med. Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland.
| | - Annerose Ziegler
- I. Med. Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland
| | - Ansgar Lohse
- I. Med. Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland
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Ye S, Liu Y, Zhao X, Ma Y, Wang Y. Hydroxychloroquine improves pregnancy outcomes of women with positive antinuclear antibody spectrum test results. Front Med (Lausanne) 2023; 10:1113127. [PMID: 37168263 PMCID: PMC10166228 DOI: 10.3389/fmed.2023.1113127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 04/05/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Empirical use of Hydroxychloroquine (HCQ) in patients with positive antinuclear antibody spectrum (ANAs) test result is controversial regarding its impact on improving perinatal outcomes. This study aimed to investigate the effect of HCQ on adverse pregnancy outcomes associated with placental dysfunction in ANAs-positive patients. METHODS The study included pregnant women with positive ANAs test result from 2016 to 2020 in our center, and divided into a weakly positive and a positive group in just ANA positive patients among them. Univariate and multivariate analyses were conducted to determine the effect of HCQ on pregnancy outcomes in each subgroup. Stratified and interactive analyses were performed to assess the value of HCQ in improving pregnancy outcomes. RESULTS (i) A total of 261 cases were included, accounting for 30.60% of pregnancy complicated with autoimmune abnormalities, and 65.12% of them used HCQ during pregnancy. (ii) The application of HCQ significantly reduced the incidence of early-onset preeclampsia (1.18% vs. 12.09%, p = 0.040) and small-for-gestational-age infants (10.06% vs. 25.84%, p = 0.003) in the ANAs-positive population, increased birth weight (3075.87 ± 603.91 g vs. 2847.53 ± 773.73 g, p = 0.025), and prolonged gestation (38.43 ± 2.31 vs. 36.34 ± 5.45 weeks, p < 0.001). (iii) A total of 185 just ANA-positive patients were stratified according to titers. Among them, the rate of HCQ usage was significantly higher than that in the weakly positive group (81.03% vs. 58.27%, p = 0.003). (vi) Stratified univariate analysis showed that HCQ usage in the ANA-positive group could reduce the incidence of preeclampsia (2.13% vs. 27.27%, p = 0.019) and prolong gestation (38.29 ± 2.54 vs. 34.48 ± 7.68 weeks, p = 0.006). In the ANA-weakly positive group, HCQ significantly reduced the incidence of preeclampsia (6.76% vs. 28.30%, p = 0.002), early-onset preeclampsia (1.35% vs. 13.21%, p = 0.027), and small-for-gestational-age infants (7.89% vs. 35.19%, p < 0.001). Multivariate regression analysis showed that HCQ significantly reduced the incidence of preeclampsia in both groups. Intergroup interaction analysis showed no significant difference in the value of HCQ in reducing the incidence of preeclampsia between the two groups. CONCLUSION ANAs positivity is an important abnormal autoimmunity type in pregnancy. HCQ can be considered as a choice for improving adverse pregnancy outcomes related to placental dysfunction, such as preeclampsia, in this population.
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Affiliation(s)
| | | | | | | | - Yongqing Wang
- Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
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Ye S, Liu Y, Zhao X, Ma Y, Wang Y. Hydroxychloroquine improves pregnancy outcomes of women with positive antinuclear antibody spectrum test results. Front Med (Lausanne) 2023; 10. [DOI: pmid: 37168263.doi: 10.3389/fmed.2023.1113127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2025] Open
Abstract
Background:Empirical use of Hydroxychloroquine (HCQ) in patients with positive antinuclear antibody spectrum (ANAs) test result is controversial regarding its impact on improving perinatal outcomes. This study aimed to investigate the effect of HCQ on adverse pregnancy outcomes associated with placental dysfunction in ANAs-positive patients.Methods:The study included pregnant women with positive ANAs test result from 2016 to 2020 in our center, and divided into a weakly positive and a positive group in just ANA positive patients among them. Univariate and multivariate analyses were conducted to determine the effect of HCQ on pregnancy outcomes in each subgroup. Stratified and interactive analyses were performed to assess the value of HCQ in improving pregnancy outcomes.Results:(i) A total of 261 cases were included, accounting for 30.60% of pregnancy complicated with autoimmune abnormalities, and 65.12% of them used HCQ during pregnancy. (ii) The application of HCQ significantly reduced the incidence of early-onset preeclampsia (1.18% vs. 12.09%, p = 0.040) and small-for-gestational-age infants (10.06% vs. 25.84%, p = 0.003) in the ANAs-positive population, increased birth weight (3075.87 ± 603.91 g vs. 2847.53 ± 773.73 g, p = 0.025), and prolonged gestation (38.43 ± 2.31 vs. 36.34 ± 5.45 weeks, p < 0.001). (iii) A total of 185 just ANA-positive patients were stratified according to titers. Among them, the rate of HCQ usage was significantly higher than that in the weakly positive group (81.03% vs. 58.27%, p = 0.003). (vi) Stratified univariate analysis showed that HCQ usage in the ANA-positive group could reduce the incidence of preeclampsia (2.13% vs. 27.27%, p = 0.019) and prolong gestation (38.29 ± 2.54 vs. 34.48 ± 7.68 weeks, p = 0.006). In the ANA-weakly positive group, HCQ significantly reduced the incidence of preeclampsia (6.76% vs. 28.30%, p = 0.002), early-onset preeclampsia (1.35% vs. 13.21%, p = 0.027), and small-for-gestational-age infants (7.89% vs. 35.19%, p < 0.001). Multivariate regression analysis showed that HCQ significantly reduced the incidence of preeclampsia in both groups. Intergroup interaction analysis showed no significant difference in the value of HCQ in reducing the incidence of preeclampsia between the two groups.Conclusion:ANAs positivity is an important abnormal autoimmunity type in pregnancy. HCQ can be considered as a choice for improving adverse pregnancy outcomes related to placental dysfunction, such as preeclampsia, in this population.
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Anti-dsDNA Is Associated with Favorable Prognosis in Myasthenia Gravis: A Retrospective Study. Acta Neurol Scand 2023. [DOI: 10.1155/2023/8939083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Objectives. To investigate the presence of serum antinuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA) in patients with myasthenia gravis (MG) and analyze the clinical characteristics and prognostic factors associated with MG. Methods. We retrospectively enrolled 363 patients with MG and analyzed the clinical characteristics and follow-up data between patients positive and negative for ANA and anti-dsDNA. We defined a Myasthenia Gravis Activities of Daily Living (MG-ADL) reduction as a main prognosis predictor and used logistic regression to determine independent factors associated with prognosis. We built a nomogram to predict prognosis and evaluate the internal validity of the model. Results. Ninety-eight (27.0%) patients were positive for ANA, and 51 (14.0%) were positive for anti-dsDNA. Patients positive for ANA and anti-dsDNA antibodies tended to be female and positive for acetylcholine receptor antibody (AChR-Ab). The rate of thymoma was higher in anti-dsDNA-positive patients with MG (p-dsDNA-MG) than in patients negative for anti-dsDNA (49.0% vs. 26.0%,
), and p-dsDNA-MG was associated with reduced MG-ADL score. Regression analysis showed that except for age of onset (
,
,
), anti-dsDNA (
,
,
), ptosis (
,
,
), and eye movement disorder (
,
,
) were independent predictive factors of a favorable prognosis of MG. These predictors were used to generate a nomogram with an excellent predictive value. Conclusions. Being female and the presence of AChR-Ab were features of ANA- or anti-dsDNA-positive MG. The presence of anti-dsDNA was associated with a favorable prognosis of MG.
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Staruszkiewicz M, Pituch-Noworolska A, Skoczen S. Uncommon types of autoantibodies - Detection and clinical associations. Autoimmun Rev 2023; 22:103263. [PMID: 36563770 DOI: 10.1016/j.autrev.2022.103263] [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: 11/18/2022] [Accepted: 12/18/2022] [Indexed: 12/24/2022]
Abstract
Immunofluorescence is a basic method for detection of autoantibodies in serum. It is used as screening for people with symptoms suggesting autoimmune process and disease. Antinuclear antibodies (ANA) assay detecting antibodies against nuclear proteins used commonly for diagnosis of systemic autoimmune disease, although antibodies against cytoplasmic components and mitotic structures are usable in clinic. The majority of ANA nuclear patterns have been comprehensively studied with increasing data. However, the cytoplasmic and mitotic patterns are underestimated and still require further assessment. In this review the clinical associations and significance of uncommon types of autoantibodies are presented and discussed.
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Affiliation(s)
| | | | - Szymon Skoczen
- Department of Paediatric Oncology and Haematology, Jagiellonian University, Medical College, Krakow, Poland; Department of Oncology and Haematology, University Children's Hospital, Krakow, Poland.
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11
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Lanzolla G, Puccinelli L, Giudetti M, Comi S, Menconi F, Maglionico MN, Posarelli C, Figus M, Marcocci C, Marinò M. Anti-nuclear autoantibodies in Graves' disease and Graves' orbitopathy. J Endocrinol Invest 2023; 46:337-344. [PMID: 36030301 PMCID: PMC9859920 DOI: 10.1007/s40618-022-01906-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 08/18/2022] [Indexed: 01/25/2023]
Abstract
OBJECTIVE A relationship between thyroid and non-organ-specific autoimmunity could be relevant for Graves' orbitopathy (GO), which affects connective tissue. We investigated the association between GO and anti-nuclear antibodies (ANAs). METHODS Retrospective investigation was conducted in 265 patients with Graves' disease (GD), 158 with and 107 without GO. Primary outcome was: prevalence of ANAs in GO vs no-GO. Secondary outcomes were: (1) relationship between ANAs and GO features; (2) prevalence of ANAs in GD compared with non-autoimmune hyperthyroidism [(78 patients with toxic nodular goiter (TNG)]; (3) distribution of ANA patterns. RESULTS ANAs were detected in 212 (80%) GD patients, but prevalence did not differ between GO (79.7%) and no-GO (80.3%). Higher ANA titers (1:160) were more common in GO (51.5 vs 38.3%), but only nearly significantly (OR 0.5; 95% CI: 0.3-1; P = 0.059). Proptosis was lower in ANA-positive patients (mean difference: - 1.4 mm; 95% CI from - 2.5 to - 0.3; P = 0.011), in whom nearly significantly lower CAS (Mann-Whitney U: 1.5; P = 0.077) and eyelid aperture (mean difference: - 0.9 mm; 95% CI from - 2 to 0; P = 0.062) were observed. Prevalence of ANAs in GD was lower than in TNG (80 vs 91%; OR 0.3; 95% CI: 0.1-0.9; P = 0.028), but nuclear speckled pattern was more frequent (OR 22.9; 95% CI 1.3-381.3; P = 0.028). CONCLUSIONS Although ANAs are not more frequent in GO, they seem to exert a protective role on its severity and on development of GD. A switch of T cell population in ANA-positive patients, resulting in a different phenotype, may be responsible. Further studies are needed to investigate the mechanisms.
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Affiliation(s)
- G Lanzolla
- Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - L Puccinelli
- Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - M Giudetti
- Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - S Comi
- Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - F Menconi
- Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - M N Maglionico
- Department of Surgical, Medical and Molecular Pathology, Ophthalmology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - C Posarelli
- Department of Surgical, Medical and Molecular Pathology, Ophthalmology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - M Figus
- Department of Surgical, Medical and Molecular Pathology, Ophthalmology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - C Marcocci
- Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy
| | - M Marinò
- Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
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12
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Antinuclear antibodies in healthy population: Positive association with abnormal tissue metabolism, inflammation and immune dysfunction. Int Immunopharmacol 2022; 113:109292. [DOI: 10.1016/j.intimp.2022.109292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/18/2022] [Accepted: 09/25/2022] [Indexed: 11/05/2022]
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13
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Alserawan L, Anguera G, Zamora Atenza C, Serra López J, Martínez-Martínez L, Riudavets Melià M, Sullivan I, Barba Joaquin A, Majem Tarruella M, Vidal S. Association between Changes in the Patterns of Antinuclear Autoantibodies during Immune Checkpoint Inhibition Therapy and the Development of Severe Immune Related Adverse Events. Int J Mol Sci 2022; 23:12641. [PMID: 36293498 PMCID: PMC9604501 DOI: 10.3390/ijms232012641] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/16/2022] [Accepted: 10/18/2022] [Indexed: 11/16/2022] Open
Abstract
Immune-related adverse events (irAEs) are unpredictable autoimmune-like toxicities induced by immune checkpoint inhibitors (ICI). irAEs are a consequence of a breakdown in self-tolerance. ICIs can induce autoantibody formation, and the presence of antinuclear autoantibodies (ANAs) has been reported in patients who developed irAEs. Our goal was to compare ANA patterns by indirect immunofluorescence at different timepoints before (baseline) and after the initiation of ICI treatment and to analyze the role of ANA pattern changes as predictors of irAEs. This is a 2-year-follow-up prospective study of 152 consecutive patients with solid tumors treated with anti-PD-(L)1 blockade agents. They were included from September 2018 until March 2020 in the Hospital de la Santa Creu I Sant Pau (Barcelona, Spain). We grouped patients into three groups: ANA de novo (patients who showed new ANA patterns at any time after ICI initiation), ANA (ANA positive at baseline without changes in the ANA patterns after initiation of treatment) and non-ANA (ANA negative at baseline and after ICI initiation). We did not find any association between the appearance of ANAs and irAE rates or the number and types of irAEs. However, patients in the ANA de novo group showed higher severe irAE rates (grade ≥ 3) than the other groups. Additionally, in most of the patients with severe irAEs (83.3%), changes in ANA patterns preceded irAE onset. In conclusion, we found ANA induction during ICI therapies in 22 patients and our results suggest that the appearance of ANAs may predict the severity of the irAE.
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Affiliation(s)
- Leticia Alserawan
- Immunology-Inflammatory Diseases, Biomedical Research Institut Sant Pau, IIB Sant Pau, 08026 Barcelona, Spain
| | - Geòrgia Anguera
- Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 Barcelona, Spain
| | - Carlos Zamora Atenza
- Immunology-Inflammatory Diseases, Biomedical Research Institut Sant Pau, IIB Sant Pau, 08026 Barcelona, Spain
| | - Jorgina Serra López
- Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 Barcelona, Spain
| | - Laura Martínez-Martínez
- Department of Immunology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08026 Barcelona, Spain
| | - Mariona Riudavets Melià
- Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 Barcelona, Spain
| | - Ivana Sullivan
- Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 Barcelona, Spain
| | - Andrés Barba Joaquin
- Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 Barcelona, Spain
| | | | - Silvia Vidal
- Immunology-Inflammatory Diseases, Biomedical Research Institut Sant Pau, IIB Sant Pau, 08026 Barcelona, Spain
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14
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Meng J, Yang G, Li S, Luo Y, Bai Y, Deng C, Song N, Li M, Zeng X, Hu C. The clinical value of indirect immunofluorescence for screening anti-rods and rings antibodies: A retrospective study of two centers in China. Front Immunol 2022; 13:1007257. [PMID: 36238277 PMCID: PMC9552219 DOI: 10.3389/fimmu.2022.1007257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 09/08/2022] [Indexed: 11/22/2022] Open
Abstract
Objective To investigate the distribution and clinical significance of the rods and rings (RR) pattern in various diseases. Methods A total of 169,891 patients in Peking Union Medical College Hospital (PUMCH) and 29,458 patients in Inner Mongolia People’s Hospital (IMPH) from January 2018 to December 2020 were included, and the results of ANA (antinuclear antibodies) and special antibodies were analyzed retrospectively. Results The positive rates of ANA and RR patterns were 34.84%, 0.16% in PUMCH, and 44.73%, 0.23% in IMPH. Anti-RR antibodies mainly appear in adults (≥ 41 years), mostly of low or medium fluorescence titers. Isolated RR patterns were mostly presented (60.30% and 69.12%, respectively), and the RR pattern mixed with the speckled pattern was most commonly observed among patients having two or more patterns. The RR pattern existed in a variety of diseases including hepatitis C, AIDs, pulmonary diseases, nephropathy diseases, and even healthy people. The highest prevalence of the RR pattern was observed in hepatic diseases, such as hepatic dysfunction (0.79%), hepatic cirrhosis (1.05%), PBC (0.85%), and AIH (0.65%), etc. The positive rate of specific antibodies in RR pattern cases was 31.25%, and anti-Ro52 (27, 20.61%) was the most common target antibody. Conclusion The RR pattern had a low prevalence in ANAs test samples and varied in different nationalities and regions. Except for hepatitis C, it could be observed in AIDs, pulmonary diseases, nephropathy, other hepatic diseases, and even healthy people, but the positive rate was slightly higher in hepatic diseases. Its mechanism of action and clinical relevance still need clarification.
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Affiliation(s)
- Jingjing Meng
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
- Department of Clinical Laboratory, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guoxiang Yang
- Department of Clinical Laboratory, Inner Mongolia People’s Hospital, Hohhot, China
| | - Siting Li
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Yueming Luo
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
- Jiangmen Wuyi Hospital of Traditional Chinese Medicine (TCM) (Affiliated Jiangmen TCM Hospital of Ji’nan University), Jiangmen, China
| | - Yina Bai
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Chuiwen Deng
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Ning Song
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
- *Correspondence: Chaojun Hu, ; Xiaofeng Zeng,
| | - Chaojun Hu
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China
- *Correspondence: Chaojun Hu, ; Xiaofeng Zeng,
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Zhang T, Chen J, Lu Y, Yang X, Ouyang Z. Identification of technology frontiers of artificial intelligence-assisted pathology based on patent citation network. PLoS One 2022; 17:e0273355. [PMID: 35994484 PMCID: PMC9394838 DOI: 10.1371/journal.pone.0273355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/05/2022] [Indexed: 12/04/2022] Open
Abstract
OBJECTIVES This paper aimed to identify the technology frontiers of artificial intelligence-assisted pathology based on patent citation network. METHODS Patents related to artificial intelligence-assisted pathology were searched and collected from the Derwent Innovation Index (DII), which were imported into Derwent Data Analyzer (DDA, Clarivate Derwent, New York, NY, USA) for authority control, and imported into the freely available computer program Ucinet 6 for drawing the patent citation network. The patent citation network according to the citation relationship could describe the technology development context in the field of artificial intelligence-assisted pathology. The patent citations were extracted from the collected patent data, selected highly cited patents to form a co-occurrence matrix, and built a patent citation network based on the co-occurrence matrix in each period. Text clustering is an unsupervised learning method, an important method in text mining, where similar documents are grouped into clusters. The similarity between documents are determined by calculating the distance between them, and the two documents with the closest distance are combined. The method of text clustering was used to identify the technology frontiers based on the patent citation network, which was according to co-word analysis of the title and abstract of the patents in this field. RESULTS 1704 patents were obtained in the field of artificial intelligence-assisted pathology, which had been currently undergoing three stages, namely the budding period (1992-2000), the development period (2001-2015), and the rapid growth period (2016-2021). There were two technology frontiers in the budding period (1992-2000), namely systems and methods for image data processing in computerized tomography (CT), and immunohistochemistry (IHC), five technology frontiers in the development period (2001-2015), namely spectral analysis methods of biomacromolecules, pathological information system, diagnostic biomarkers, molecular pathology diagnosis, and pathological diagnosis antibody, and six technology frontiers in the rapid growth period (2016-2021), namely digital pathology (DP), deep learning (DL) algorithms-convolutional neural networks (CNN), disease prediction models, computational pathology, pathological image analysis method, and intelligent pathological system. CONCLUSIONS Artificial intelligence-assisted pathology was currently in a rapid development period, and computational pathology, DL and other technologies in this period all involved the study of algorithms. Future research hotspots in this field would focus on algorithm improvement and intelligent diagnosis in order to realize the precise diagnosis. The results of this study presented an overview of the characteristics of research status and development trends in the field of artificial intelligence-assisted pathology, which could help readers broaden innovative ideas and discover new technological opportunities, and also served as important indicators for government policymaking.
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Affiliation(s)
- Ting Zhang
- Institute of Medical Information & Library, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Juan Chen
- Institute of Medical Information & Library, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Yan Lu
- Institute of Medical Information & Library, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Xiaoyi Yang
- Institute of Medical Information & Library, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Zhaolian Ouyang
- Institute of Medical Information & Library, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
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16
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Chepy A, Bourel L, Koether V, Launay D, Dubucquoi S, Sobanski V. Can Antinuclear Antibodies Have a Pathogenic Role in Systemic Sclerosis? Front Immunol 2022; 13:930970. [PMID: 35837382 PMCID: PMC9274282 DOI: 10.3389/fimmu.2022.930970] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 05/26/2022] [Indexed: 12/30/2022] Open
Abstract
Systemic sclerosis (SSc) is a connective tissue disease characterized by extensive fibrosis of the skin and internal organs, associated with vasculopathy and autoimmune features. Antinuclear antibodies (ANA) are found in almost all SSc patients and constitute strong diagnosis and prognosis biomarkers. However, it remains unclear whether ANA are simple bystanders or if they can have a role in the pathophysiology of the disease. One might think that the nuclear nature of their targets prevents any accessibility to autoantibodies. Nevertheless, recent data suggest that ANA could be pathogenic or at least contribute to the perennation of the disease. We review here first the indirect clues of the contribution of ANA to SSc: they are associated to the disease subtypes, they may precede disease onset, their titer correlates with disease activity and severity, there is an association between molecular subsets, and some patients can respond to B-cell targeting therapy. Then, we describe in a second part the mechanisms of ANA production in SSc from individual genetic background to post-transcriptional modifications of neoantigens. Finally, we elaborate on the potential mechanisms of pathogenicity: ANA could be pathogenic through immune-complex-mediated mechanisms; other processes potentially involve molecular mimicry and ANA penetration into the target cell, with a focus on anti-topoisomerase-I antibodies, which are the most probable candidate to play a role in the pathophysiology of SSc. Finally, we outline some technical and conceptual ways to improve our understanding in this field.
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Affiliation(s)
- Aurélien Chepy
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, France
| | - Louisa Bourel
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
| | - Vincent Koether
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, France
| | - David Launay
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, France
| | - Sylvain Dubucquoi
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Institut d’Immunologie, Lille, France
| | - Vincent Sobanski
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, France
- Institut Universitaire de France (IUF), Paris, France
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17
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Andersen CJ, Vance TM. Sex-Specific Associations Between Serum Lipids, Antinuclear Antibodies, and Statin Use in National Health and Nutrition Examination Surveys 1999-2004. Front Med (Lausanne) 2022; 9:887741. [PMID: 35721098 PMCID: PMC9198832 DOI: 10.3389/fmed.2022.887741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 04/26/2022] [Indexed: 12/04/2022] Open
Abstract
Lipid metabolism contributes to the regulation of leukocyte activity and immune responses, and may serve as a therapeutic target in the pathophysiology and clinical management of autoimmune disorders. In addition to lipid-lowering properties, statins have been shown to exert anti-inflammatory and immunomodulatory effects within the context of autoimmunity. Importantly, autoimmune incidence and lipid markers differ between men and women, suggesting that the relationship between lipid metabolism and immune function may vary by sex. Therefore, we investigated whether a predictive, sex-specific relationship exists between serum lipids, statin use, and antinuclear antibodies (ANA)—a routine clinical marker of autoimmunity and immune dysfunction—in U.S. men and women (>20 years old; n = 1,526) from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Within this population, a greater proportion of women were positive for ANA (ANA+) and had higher ANA titers, as compared to men. While we did not observe statistical differences in average total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), or triglyceride levels in ANA positive (ANA+) vs. ANA negative (ANA–) men or women, we observed that a greater proportion of ANA+ women had high total cholesterol levels (>240 mg/dL) when compared to ANA+ men (13.0 vs. 9.0%), and that a greater percentage of ANA+ women had low HDL-C as compared to ANA+ men (29.2 vs. 19.6%). However, in logistic regression models, total cholesterol, LDL-C, and HDL-C levels were not able to predict ANA status, whereas elevated serum triglycerides (150 to < 200 mg/dL) were significantly less likely to be ANA+ vs. ANA– (OR 0.33; 95% CI 0.11–0.92) in men only. Interestingly, women who reported taking statins have significantly lower odds of being ANA+ (OR 0.25; 95% CI 0.09–0.76), whereas no significant association between statin use and ANA status was observed in men. Together, our findings provide novel insight into the relationship between lipid metabolism and autoimmunity by elucidating the limited, albeit sex-specific utility of routine clinical serum lipid levels to predict ANA status at the population level, while further identifying a sex-specific and protective role for statins in predicting ANA status in women.
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Affiliation(s)
- Catherine J Andersen
- Department of Biology, Fairfield University, Fairfield, CT, United States.,Department of Nutritional Sciences, University of Connecticut, Storrs, CT, United States
| | - Terrence M Vance
- Department of Exercise and Nutrition Sciences, The State University of New York Plattsburgh, Plattsburgh, NY, United States
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18
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Moura RA, Fonseca JE. B Cells on the Stage of Inflammation in Juvenile Idiopathic Arthritis: Leading or Supporting Actors in Disease Pathogenesis? Front Med (Lausanne) 2022; 9:851532. [PMID: 35449805 PMCID: PMC9017649 DOI: 10.3389/fmed.2022.851532] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 02/09/2022] [Indexed: 11/13/2022] Open
Abstract
Juvenile idiopathic arthritis (JIA) is a term that collectively refers to a group of chronic childhood arthritides, which together constitute the most common rheumatic condition in children. The International League of Associations for Rheumatology (ILAR) criteria define seven categories of JIA: oligoarticular, polyarticular rheumatoid factor (RF) negative (RF-), polyarticular RF positive (RF+), systemic, enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. The ILAR classification includes persistent and extended oligoarthritis as subcategories of oligoarticular JIA, but not as distinct categories. JIA is characterized by a chronic inflammatory process affecting the synovia that begins before the age of 16 and persists at least 6 weeks. If not treated, JIA can cause significant disability and loss of quality of life. Treatment of JIA is adjusted according to the severity of the disease as combinations of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and/ or biological disease modifying anti-rheumatic drugs (DMARDs). Although the disease etiology is unknown, disturbances in innate and adaptive immune responses have been implicated in JIA development. B cells may have important roles in JIA pathogenesis through autoantibody production, antigen presentation, cytokine release and/ or T cell activation. The study of B cells has not been extensively explored in JIA, but evidence from the literature suggests that B cells might have indeed a relevant role in JIA pathophysiology. The detection of autoantibodies such as antinuclear antibodies (ANA), RF and anti-citrullinated protein antibodies (ACPA) in JIA patients supports a breakdown in B cell tolerance. Furthermore, alterations in B cell subpopulations have been documented in peripheral blood and synovial fluid from JIA patients. In fact, altered B cell homeostasis, B cell differentiation and B cell hyperactivity have been described in JIA. Of note, B cell depletion therapy with rituximab has been shown to be an effective and well-tolerated treatment in children with JIA, which further supports B cell intervention in disease development.
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Affiliation(s)
- Rita A Moura
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - João Eurico Fonseca
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.,Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte (CHULN), Lisbon Academic Medical Centre, Lisbon, Portugal
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Barreno-Rocha SG, Guzmán-Silahua S, Rodríguez-Dávila SDC, Gavilanez-Chávez GE, Cardona-Muñoz EG, Riebeling-Navarro C, Rubio-Jurado B, Nava-Zavala AH. Antiphospholipid Antibodies and Lipids in Hematological Malignancies. Int J Mol Sci 2022; 23:ijms23084151. [PMID: 35456969 PMCID: PMC9025841 DOI: 10.3390/ijms23084151] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/06/2022] [Accepted: 04/07/2022] [Indexed: 02/01/2023] Open
Abstract
One of the main groups of lipids is phospholipids, which are mainly involved in forming cell membranes. Neoplastic processes such as cell replication have increased lipid synthesis, making tumor cells dependent on this synthesis to maintain their requirements. Antiphospholipid antibodies attack phospholipids in the cell membranes. Three main types of antiphospholipid antibodies are recognized: anti-β2 glycoprotein I (anti-β2GP-I), anticardiolipin (aCL), and lupus anticoagulant (LA). These types of antibodies have been proven to be present in hematological neoplasms, particularly in LH and NHL. This review on antiphospholipid antibodies in hematological neoplasms describes their clinical relationship as future implications at the prognostic level for survival and even treatment.
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Affiliation(s)
- Sonia Guadalupe Barreno-Rocha
- Unidad de Investigación Epidemiológica y en Servicios de Salud, CMNO OOAD Jalisco Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico; (S.G.B.-R.); (S.G.-S.); (S.-d.-C.R.-D.); (G.E.G.-C.)
- Programa de Doctorado en Farmacología, Departamento de Fisiología, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico;
| | - Sandra Guzmán-Silahua
- Unidad de Investigación Epidemiológica y en Servicios de Salud, CMNO OOAD Jalisco Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico; (S.G.B.-R.); (S.G.-S.); (S.-d.-C.R.-D.); (G.E.G.-C.)
- Programa de Doctorado en Farmacología, Departamento de Fisiología, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico;
| | - Sinaí-del-Carmen Rodríguez-Dávila
- Unidad de Investigación Epidemiológica y en Servicios de Salud, CMNO OOAD Jalisco Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico; (S.G.B.-R.); (S.G.-S.); (S.-d.-C.R.-D.); (G.E.G.-C.)
| | - Guadalupe Estela Gavilanez-Chávez
- Unidad de Investigación Epidemiológica y en Servicios de Salud, CMNO OOAD Jalisco Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico; (S.G.B.-R.); (S.G.-S.); (S.-d.-C.R.-D.); (G.E.G.-C.)
- Programa de Doctorado en Farmacología, Departamento de Fisiología, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico;
| | - Ernesto Germán Cardona-Muñoz
- Programa de Doctorado en Farmacología, Departamento de Fisiología, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico;
| | - Carlos Riebeling-Navarro
- Unidad de Investigación en Epidemiologia Clínica, UMAE HP CMN-SXXI, Ciudad de México 06720, Mexico;
| | - Benjamín Rubio-Jurado
- Unidad de Investigación Epidemiológica y en Servicios de Salud, CMNO OOAD Jalisco Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico; (S.G.B.-R.); (S.G.-S.); (S.-d.-C.R.-D.); (G.E.G.-C.)
- Departamento Clínico de Hematología, División Onco-Hematologia, UMAE, Hospital de Especialidades, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico
- Correspondence: (B.R.-J.); (A.H.N.-Z.)
| | - Arnulfo Hernán Nava-Zavala
- Unidad de Investigación Epidemiológica y en Servicios de Salud, CMNO OOAD Jalisco Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico; (S.G.B.-R.); (S.G.-S.); (S.-d.-C.R.-D.); (G.E.G.-C.)
- Programa Internacional de Medicina, Universidad Autónoma de Guadalajara, Guadalajara 44670, Mexico
- Departamento de Inmunología y Reumatología del Hospital General de Occidente, Secretaría de Salud Jalisco, Guadalajara 45070, Mexico
- Correspondence: (B.R.-J.); (A.H.N.-Z.)
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20
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García MJ, Rodríguez-Duque JC, Pascual M, Rivas C, Castro B, Raso S, López-Hoyos M, Arias-Loste MT, Rivero M. Prevalence of antinuclear antibodies in inflammatory bowel disease and seroconversion after biological therapy. Therap Adv Gastroenterol 2022; 15:17562848221077837. [PMID: 35251307 PMCID: PMC8894967 DOI: 10.1177/17562848221077837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 01/13/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Estimates of detectable antinuclear antibodies (ANA) prevalence vary widely, from 6% in healthy populations to 50-80% in patients with autoimmune disease. However, there is a lack of evidence about the overall prevalence in inflammatory bowel disease (IBD) and ANA seroconversion after the beginning of biological therapy. OBJECTIVES The aim of the study was to investigate the overall prevalence of ANA in IBD patients, their relationship with different treatments, clinical outcomes and the seroconversion rate of ANA in patients treated with biological therapy. METHODS Ambispective observational study including all consecutive IBD patients was carried out. Information about the presence of ANA, disease phenotype, duration, activity, complications, and past and current treatments were transversally collected. Retrospectively, in patients with detectable ANA, data regarding previous ANA detection and the diagnosis of lupus-like syndrome (LLS) was gathered. RESULTS A total of 879 IBD patients were included. We observed a detectable ANA prevalence of 13.6%. The presence of ANA was frequently associated with biological therapy (36/118) and decreased when immunomodulators were combined to this therapy (7/32). Of 78 patients with ANA prior to the beginning of biological therapy, a seroconversion rate of 28.8% was observed after a mean of 3.14 years. Only 1 patient suffered LLS. CONCLUSION Our study showed a prevalence of detectable ANA higher than the expected in healthy population. The presence of ANA was lower when immunomodulator therapy is associated. The ANA seroconversion rate is relevant after the initiation of biological treatment nevertheless, the risk of LLS appeared to be marginal.
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Affiliation(s)
| | | | - Marta Pascual
- Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain,Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Instituto de Investigación Sanitaria de Valdecilla (IDIVAL), Santander, Spain
| | - Coral Rivas
- Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain,Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Instituto de Investigación Sanitaria de Valdecilla (IDIVAL), Santander, Spain
| | - Beatriz Castro
- Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain,Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Instituto de Investigación Sanitaria de Valdecilla (IDIVAL), Santander, Spain
| | - Sandra Raso
- Immunology Department, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria de Valdecilla (IDIVAL), Santander, Spain
| | - Marcos López-Hoyos
- Immunology Department, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria de Valdecilla (IDIVAL), Santander, Spain
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21
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Zhou W, Wang X, Chang J, Cheng C, Miao C. The molecular structure and biological functions of RNA methylation, with special emphasis on the roles of RNA methylation in autoimmune diseases. Crit Rev Clin Lab Sci 2021; 59:203-218. [PMID: 34775884 DOI: 10.1080/10408363.2021.2002256] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic vasculitis are caused by the body's immune response to autoantigens. The pathogenesis of autoimmune diseases is complex. RNA methylation is known to play a key role in disease progression as it regulates almost all aspects of RNA processing, including RNA nuclear export, translation, splicing, and noncoding RNA processing. This review summarizes the mechanisms, molecular structures of RNA methylations and their roles in biological functions. Similar to the roles of RNA methylation in cancers, RNA methylation in RA and SLE involves "writers" that deposit methyl groups to form N6-methyladenosine (m6A) and 5-methylcytosine (m5C), "erasers" that remove these modifications, and "readers" that further affect mRNA splicing, export, translation, and degradation. Recent advances in detection methods have identified N1-methyladenosine (m1A), N6,2-O-dimethyladenosine (m6Am), and 7-methylguanosine (m7G) RNA modifications, and their roles in RA and SLE need to be further studied. The relationship between RNA methylation and other autoimmune diseases has not been reported, and the roles and mechanisms of RNA modifications in these diseases need to be explored in the future.
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Affiliation(s)
- Wanwan Zhou
- Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Xiao Wang
- Department of Clinical Nursing, School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Jun Chang
- Department of Orthopaedics, Fourth Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
| | - Chenglong Cheng
- Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Chenggui Miao
- Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, China.,Institute of Prevention and Treatment of Rheumatoid Arthritis, Anhui University of Chinese Medicine, Hefei, Anhui, China.,Department of Pharmacy, School of Life and Health Sciences, Anhui University of Science and Technology, Fengyang, Anhui Province, China
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22
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Xiao Y, Lin Y, Zhang Y, Wang J, Zeng Y. Factors associated with the antinuclear antibody (ANA) titer of systemic autoimmune rheumatic diseases in ANA-positive patients after treatment: a retrospective study. Clin Exp Med 2021; 22:439-446. [PMID: 34542782 DOI: 10.1007/s10238-021-00759-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 08/28/2021] [Indexed: 01/21/2023]
Abstract
Antinuclear antibodies (ANAs) are a serological hallmark of systemic autoimmune rheumatic diseases (SARDs); however, few studies have investigated their post-treatment levels. The mechanism by which ANA titers are upregulated in SARDs remains unclear. We assessed factors associated with the ANA titer after treatment. In this retrospective study, we analyzed the clinical database of Zhongshan Hospital, Medical College of Xiamen. Demographic data and baseline and 12-month post-treatment ANA titers were collected. Bivariate and multivariate analyses were performed to determine the factors associated with the ANA titer. This study identified 31,923 patients who underwent ANA assay for SARDs screening, and a total of 1043 patients were included in the study. Approximately 16% of the patients showed a decrease in the serological ANA titer. Younger patients (< 20) were 3 × more likely to experience such a decrease (P = 0.005) compared to older patients (≥ 60 years). Having a baseline ANA titer > 1:10,000 was associated with an increase likelihood of a decrease in the serological ANA titer compared with baseline ANA titer 1:10,000, 1:3200 and 1:1000 (P < 0.001). We found that a decrease in the serum ANA titer at 12 months after treatment for SARDs is associated with age and ANA baseline titers.
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Affiliation(s)
- Yun Xiao
- Center of Clinical Laboratory, School of Medicine, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.,Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China
| | - Yiqiang Lin
- Center of Clinical Laboratory, School of Medicine, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.,Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China
| | - Yan Zhang
- Center of Clinical Laboratory, School of Medicine, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.,Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China
| | - Jiajia Wang
- Center of Clinical Laboratory, School of Medicine, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.,Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China
| | - Yanli Zeng
- Center of Clinical Laboratory, School of Medicine, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China. .,Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China.
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23
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Properties of Uncommon Indirect Immunofluorescence Staining Patterns Determined during Antinuclear Antibody Detection on HEp-2 Cells. J Clin Med 2021; 10:jcm10173866. [PMID: 34501315 PMCID: PMC8432039 DOI: 10.3390/jcm10173866] [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: 07/20/2021] [Revised: 08/22/2021] [Accepted: 08/27/2021] [Indexed: 11/16/2022] Open
Abstract
In this study, we aimed to assess the prevalence of uncommon staining patterns found during testing for the presence of antinuclear antibodies (ANA) and to determine their association with certain antibodies and clinical diagnoses. Presence of ANA and the staining pattern was determined in 10955 samples using indirect immunofluorescence (IIF) on HEp-2 cells. ANA-positive samples were assessed for presence of 14 specific antibody types using a microbead based system. Demographic data (age, sex) and clinical diagnoses were collected from the referral documentation. Particular staining patterns were then compared with a representative comparison group comprised of samples with common staining patterns using these criteria. There were 22 patterns present in less than 3% of samples each and these were jointly present in 42.43% of ANA-positive samples. Specific antibodies were found in proportions similar to the comparison group (46.06%) and varied significantly between patterns. Likewise, there were significant differences in antibody distribution in particular patterns. Some patterns were associated with presence of rheumatic diseases or inflammatory arthropathies, while in others there was a concurrent diagnosis of liver disease, or a neoplastic process. Many of the uncommon IIF patterns have distinctive characteristics that warrant further investigation in order to determine their role in diagnosing various diseases, not limited only to the illnesses of the rheumatic spectrum. IIF on HEp-2 cells remains an irreplaceable method because of the diversity of ANA, only a number of which can be detected using other standardised methods.
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24
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Pashnina IA, Krivolapova IM, Fedotkina TV, Ryabkova VA, Chereshneva MV, Churilov LP, Chereshnev VA. Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease. Antibodies (Basel) 2021; 10:9. [PMID: 33668697 PMCID: PMC8006153 DOI: 10.3390/antib10010009] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/26/2020] [Accepted: 02/07/2021] [Indexed: 12/11/2022] Open
Abstract
The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in health occurs in low concentrations, with a prevalence up to 50% in some populations, which demands a cutoff revision. This review deals with the origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions, and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as a possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing additive combinations according to the concept of the mosaic of autoimmunity. Not only are titers, but also HEp-2 IFA) staining patterns, such as AC-2, important. Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or "autoimmunodeficiency" could be the reason for disorders.
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Affiliation(s)
- Irina A. Pashnina
- Regional Children’s Clinical Hospital, 620149 Yekaterinburg, Russia;
| | - Irina M. Krivolapova
- Regional Children’s Clinical Hospital, 620149 Yekaterinburg, Russia;
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, 620049 Yekaterinburg, Russia; (M.V.C.); (V.A.C.)
| | - Tamara V. Fedotkina
- Laboratory of the Mosaics of Autoimmunity, Saint Petersburg State University, 199034 Saint Petersburg, Russia; (T.V.F.); (V.A.R.); (L.P.C.)
| | - Varvara A. Ryabkova
- Laboratory of the Mosaics of Autoimmunity, Saint Petersburg State University, 199034 Saint Petersburg, Russia; (T.V.F.); (V.A.R.); (L.P.C.)
| | - Margarita V. Chereshneva
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, 620049 Yekaterinburg, Russia; (M.V.C.); (V.A.C.)
| | - Leonid P. Churilov
- Laboratory of the Mosaics of Autoimmunity, Saint Petersburg State University, 199034 Saint Petersburg, Russia; (T.V.F.); (V.A.R.); (L.P.C.)
- Saint Petersburg Research Institute of Phthisiopulmonology, 191036 Saint Petersburg, Russia
| | - Valeriy A. Chereshnev
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, 620049 Yekaterinburg, Russia; (M.V.C.); (V.A.C.)
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25
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Amirhosseini M, Alkaissi H, Hultman PA, Havarinasab S. Autoantibodies in outbred Swiss Webster mice following exposure to gold and mercury. Toxicol Appl Pharmacol 2020; 412:115379. [PMID: 33358697 DOI: 10.1016/j.taap.2020.115379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/25/2020] [Accepted: 12/17/2020] [Indexed: 10/22/2022]
Abstract
Exposure to heavy metals may have toxic effects on several human organs causing morbidity and mortality. Metals may trigger or exacerbate autoimmunity in humans. Inbred mouse strains with certain H-2 haplotypes are susceptible to xenobiotic-induced autoimmunity; and their immune response to metals such as mercury, gold, and silver have been explored. Serum antinuclear antibodies (ANA), polyclonal B-cell activation, hypergammaglobulinemia and tissue immune complex deposition are the main features of metal-induced autoimmunity in inbred mice. However, inbred mouse strains do not represent the genetic heterogeneity in humans. In this study, outbred Swiss Webster (SW) mice exposed to gold or mercury salts showed immune and autoimmune responses. Intramuscular injection of 22.5 mg/kg.bw aurothiomalate (AuTM) induced IgG ANA in SW mice starting after 5 weeks that persisted until week 15 although with a lower intensity. This was accompanied by elevated serum levels of total IgG antibodies against chromatin and total histones. Exposure to gold led to development of serum IgG autoantibodies corresponding to H1 and H2A histones, and dsDNA. Both gold and mercury induced polyclonal B-cell activation. Eight mg/L mercuric chloride (HgCl2) in drinking water, caused IgG antinucleolar antibodies (ANoA) after 5 weeks in SW mice accompanied by immune complex deposition in kidneys and spleen. Serum IgG antibodies corresponding to anti-fibrillarin, and anti-PM/Scl-100 antibodies, were observed in mercury-exposed SW mice. Gold and mercury trigger systemic autoimmune response in genetically heterogeneous outbred SW mice and suggest them as an appropriate model to study xenobiotic-induced autoimmunity.
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Affiliation(s)
- Mehdi Amirhosseini
- Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
| | - Hammoudi Alkaissi
- Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
| | - Per A Hultman
- Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Pathology, Linköping University, Linköping, Sweden
| | - Said Havarinasab
- Division of Clinical Chemistry, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
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26
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Krumkamp R, Struck NS, Lorenz E, Zimmermann M, Boahen KG, Sarpong N, Owusu-Dabo E, Pak GD, Jeon HJ, Marks F, Jacobs T, May J, Eibach D. Classification of invasive bloodstream infections and Plasmodium falciparum malaria using autoantibodies as biomarkers. Sci Rep 2020; 10:21168. [PMID: 33273605 PMCID: PMC7712777 DOI: 10.1038/s41598-020-78155-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 11/20/2020] [Indexed: 01/25/2023] Open
Abstract
A better understanding of disease-specific biomarker profiles during acute infections could guide the development of innovative diagnostic methods to differentiate between malaria and alternative causes of fever. We investigated autoantibody (AAb) profiles in febrile children (≤ 5 years) admitted to a hospital in rural Ghana. Serum samples from 30 children with a bacterial bloodstream infection and 35 children with Plasmodium falciparum malaria were analyzed using protein microarrays (Protoplex Immune Response Assay, ThermoFisher). A variable selection algorithm was applied to identify the smallest set of AAbs showing the best performance to classify malaria and bacteremia patients. The selection procedure identified 8 AAbs of which IFNGR2 and FBXW5 were selected in repeated model run. The classification error was 22%, which was mainly due to non-Typhi Salmonella (NTS) diagnoses being misclassified as malaria. Likewise, a cluster analysis grouped patients with NTS and malaria together, but separated malaria from non-NTS infections. Both current and recent malaria are a risk factor for NTS, therefore, a better understanding about the function of AAb in disease-specific immune responses is required in order to support their application for diagnostic purposes.
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Affiliation(s)
- Ralf Krumkamp
- Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359, Hamburg, Germany.,German Centre for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
| | - Nicole Sunaina Struck
- Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359, Hamburg, Germany. .,German Centre for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.
| | - Eva Lorenz
- Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359, Hamburg, Germany.,German Centre for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
| | - Marlow Zimmermann
- Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359, Hamburg, Germany.,German Centre for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
| | - Kennedy Gyau Boahen
- Department of Infectious Disease Epidemiology, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana
| | - Nimako Sarpong
- Department of Infectious Disease Epidemiology, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana
| | - Ellis Owusu-Dabo
- School of Public Health, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana
| | - Gi Deok Pak
- Epidemiology Unit, International Vaccine Institute (IVI), Seoul, Republic of Korea
| | - Hyon Jin Jeon
- Epidemiology Unit, International Vaccine Institute (IVI), Seoul, Republic of Korea
| | - Florian Marks
- Epidemiology Unit, International Vaccine Institute (IVI), Seoul, Republic of Korea.,The Department of Medicine, the University of Cambridge, Cambridge, UK
| | - Thomas Jacobs
- Research Group Protozoa Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
| | - Jürgen May
- Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359, Hamburg, Germany.,German Centre for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.,First Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Daniel Eibach
- Department of Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359, Hamburg, Germany.,German Centre for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
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27
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Wei Q, Jiang Y, Xie J, Lv Q, Xie Y, Tu L, Xiao M, Wu Z, Gu J. Analysis of antinuclear antibody titers and patterns by using HEp-2 and primate liver tissue substrate indirect immunofluorescence assay in patients with systemic autoimmune rheumatic diseases. J Clin Lab Anal 2020; 34:e23546. [PMID: 33047841 PMCID: PMC7755809 DOI: 10.1002/jcla.23546] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 08/04/2020] [Accepted: 08/05/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Indirect immunofluorescence assay (IIFA) is viewed as a preliminary standard to assess antinuclear antibodies (ANAs). Our aim was to explore ANA positivity rate, titers, and patterns in patients with systemic autoimmune rheumatic diseases (SARD), including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), and mixed connective tissue disease (MCTD), compared with healthy controls (HC). METHODS Assess antinuclear antibody titers and patterns were retrospectively identified and compared by IIFA using human epithelial cells (HEp-2) and primate liver tissue substrate according to international consensus in SARD. Serum complement 3 (C3), C4, and immunoglobulin G were compared among subgroups with different ANA titers. The positive predictive values (PPV) for different ANA titers were calculated. RESULTS There were a total of 3510 samples, including 2034 SLE, 973 RA, 155 SSc, 309 pSS, and 39 MCTD cases. There was no difference in age between HC and SARD, excluding RA. ANA positivity rate in SARD and HC was 78.7% and 12.2%, respectively. A titer of ≥1:320 revealed a PPV of 84.0% in SARD. SLE patients with ANA titers ≥1:320 had significantly lower levels of C3 and C4. AC-4 (31.2%) was the major pattern in patients with SARD, followed by AC-5 (23.9%) and AC-1 (18.8%). SLE mostly presented with AC-4 (30.3%). Several mixed patterns provided a significant hint for SSc and SLE. The major pattern in HC was AC-2 (12.2%). CONCLUSIONS Assess antinuclear antibody positivity, titers, and patterns display differences in various SARD, contributing to the classification of SARD.
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Affiliation(s)
- Qiujing Wei
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
| | - Yutong Jiang
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
| | - Jiewen Xie
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
| | - Qing Lv
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
| | - Ya Xie
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
| | - Liudan Tu
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
| | - Min Xiao
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
| | - Zhongming Wu
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
| | - Jieruo Gu
- Department of Rheumatology and ImmunologyThird Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouChina
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28
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Clinical and serological characteristics of seronegative primary Sjögren's syndrome: a comparative study. Clin Rheumatol 2020; 40:221-229. [PMID: 32504193 DOI: 10.1007/s10067-020-05154-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/10/2020] [Accepted: 05/05/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVES This study compared the clinical and serological characteristics of seronegative and seropositive primary Sjögren syndrome (pSS) and examined whether current classification criteria for pSS cover seronegative pSS. METHODS The study group comprised 375 patients (341 women and 34 men) diagnosed with pSS. A clinical diagnosis by an expert rheumatologist was considered the "gold standard" for the diagnosis of pSS. The clinical and serological characteristics of the patients were retrospectively collected from hospital medical files. RESULTS Fifty-eight of the 375 pSS patients (15.5%) were seronegative for ANA, RF, anti-Ro, and anti-La autoantibodies. Seronegative pSS was diagnosed based on lymphocytic infiltrations in lip biopsy samples. There were no statistically significant differences in terms of patient age, age at diagnosis, sex distribution, clinical features, and laboratory findings between seronegative and seropositive pSS. The frequency of hypergammaglobulinemia was higher in seropositive pSS. The 2016 ACR/ULAR criteria best covered most seronegative pSS cases (84.5%). For seronegative pSS, the agreement between the 2002 AECG, 2012 ACR, and 2016 ACR/EULAR criteria was relatively low. CONCLUSIONS The clinical features of seronegative pSS (i.e., a lack of four autoantibodies in serum) were similar to those of seropositive pSS. The current classification criteria for pSS should not be used in the diagnosis of seronegative pSS, as the agreement between the different sets of criteria was low, and some patients fell outside the classification. Further clinical and laboratory studies are needed to identify the features that distinguish seronegative pSS. Key Points • Approximately 15% of the pSS patients were seronegative for ANA, RF, anti-Ro, and anti-La autoantibodies. • Seronegative pSS was diagnosed based on lymphocytic infiltrations in lip biopsy samples. • The clinical features of seronegative pSS were similar to those of seropositive pSS. • The current classification criteria for pSS should not be used in the diagnosis of seronegative patients, as the agreement between the different sets of criteria was low, and some patients fell outside the classification.
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Zhang B, Yang Y, Lin Y, Ai L, Men X, Lu Z. Serum Systemic Autoantibodies in Anti-N-Methyl-D-Aspartate Receptor Encephalitis. Front Neurol 2020; 11:117. [PMID: 32180757 PMCID: PMC7059175 DOI: 10.3389/fneur.2020.00117] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 02/03/2020] [Indexed: 01/01/2023] Open
Abstract
Objective: The aim of this retrospective study was to investigate the relationship between serum systemic autoantibodies and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Thirty-nine patients with anti-NMDAR encephalitis were examined for serum systemic autoantibodies (antinuclear antibodies, extractable nuclear antigen autoantibodies, rheumatoid factors, and anti-neutrophil cytoplasmic antibodies), in comparison with 39 neuromyelitis optica spectrum disorder (NMOSD) and 78 healthy controls. Clinical features, cerebrospinal fluid characteristics, and outcomes were compared between the two subgroups of anti-NMDAR patients with positive and negative systemic autoantibodies, respectively. Results: Anti-NMDAR encephalitis patients had higher frequency of positive serum systemic autoantibodies than healthy controls (23.1 vs. 2.6%, p = 0.001) and lower frequency than NMOSD (23.1 vs. 48.7%, p = 0.018). No patients were diagnosed comorbidities with non-organ-specific autoimmune diseases. Consciousness disturbance was more frequent in autoantibodies positive group than in the negative group (88.9 vs. 40.0%, p = 0.02). Autoantibody positive group had a poorer outcome than autoantibody negative group (55.6 vs. 86.7%, p = 0.043). There was a negative correlation between serum autoantibodies and outcomes in anti-NMDAR encephalitis patients (r = −0.325, p = 0.044). Conclusion: Our data demonstrated serum systemic autoantibodies were more frequent in anti-NMDAR encephalitis patients than in healthy controls and less frequent than NMOSD, which were associated with higher severity of disease.
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Affiliation(s)
- Bingjun Zhang
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu Yang
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yinyao Lin
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lulu Ai
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuejiao Men
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhengqi Lu
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Park HJ, Ko HL, Won DH, Hwang DB, Shin YS, Kwak HW, Kim HJ, Yun JW, Nam JH. Comprehensive Analysis of the Safety Profile of a Single-Stranded RNA Nano-Structure Adjuvant. Pharmaceutics 2019; 11:E464. [PMID: 31500241 PMCID: PMC6781302 DOI: 10.3390/pharmaceutics11090464] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 09/04/2019] [Accepted: 09/05/2019] [Indexed: 01/01/2023] Open
Abstract
Adjuvants enhance the efficacy of vaccines by stimulating immune response-related gene expression and pathways. Although some adjuvants have been approved for commercial use in human vaccines (e.g., Alum, MF59, and AS03), they might elicit adverse side effects, such as autoimmune diseases. Recently, we developed a novel single-stranded RNA (ssRNA) nano-structure adjuvant, which can stimulate both Th1 and Th2 responses. In this study, we evaluated the safety and toxicological profiles of this ssRNA nano-structure adjuvant in vitro and in vivo. Mice were intramuscularly immunized with the ssRNA nano-structure adjuvant three times, once every 2 weeks. The results indicate no significant differences in hematological and serum biochemistry parameters between the ssRNA-treated groups and the control group. From a histopathological perspective, no evidence of tissue damage was found in any group. The levels of IgE and anti-nuclear antibodies, which are markers of autoimmune disease, were not different between the ssRNA-treated groups and the control group. The findings of this study suggest that the ssRNA nano-structure can be used as a safe adjuvant to increase vaccine efficacies.
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Affiliation(s)
- Hyeong-Jun Park
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
| | - Hae Li Ko
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
| | - Dong-Hoon Won
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
| | - Da-Bin Hwang
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
| | - Yoo-Sub Shin
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
| | - Hye-Won Kwak
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
| | - Hye-Jung Kim
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
| | - Jun-Won Yun
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
| | - Jae-Hwan Nam
- Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea.
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Mazón-Cabrera R, Vandormael P, Somers V. Antigenic Targets of Patient and Maternal Autoantibodies in Autism Spectrum Disorder. Front Immunol 2019; 10:1474. [PMID: 31379804 PMCID: PMC6659315 DOI: 10.3389/fimmu.2019.01474] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 06/13/2019] [Indexed: 12/13/2022] Open
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose behavioral symptoms become apparent in early childhood. The underlying pathophysiological mechanisms are only partially understood and the clinical manifestations are heterogeneous in nature, which poses a major challenge for diagnosis, prognosis and intervention. In the last years, an important role of a dysregulated immune system in ASD has emerged, but the mechanisms connecting this to a disruption of brain development are still largely unknown. Although ASD is not considered as a typical autoimmune disease, self-reactive antibodies or autoantibodies against a wide variety of targets have been found in a subset of ASD patients. In addition, autoantibodies reactive to fetal brain proteins have also been described in the prenatal stage of neurodevelopment, where they can be transferred from the mother to the fetus by transplacental transport. In this review, we give an extensive overview of the antibodies described in ASD according to their target antigens, their different origins, and timing of exposure during neurodevelopment.
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Affiliation(s)
| | | | - Veerle Somers
- Biomedical Research Institute, Faculty of Medicine and Life Science, Hasselt University, Diepenbeek, Belgium
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