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1
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Passam FH, Chen G, Chen VM, Qi M, Krilis SA, Giannakopoulos B. Βeta-2-glycoprotein I exerts antithrombotic function through its domain V in mice. J Autoimmun 2021; 126:102747. [PMID: 34794103 DOI: 10.1016/j.jaut.2021.102747] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 11/03/2021] [Accepted: 11/07/2021] [Indexed: 11/26/2022]
Abstract
Little is known about the physiological role of beta-2-glycoprotein I (β2GPI) despite it being the major auto-antigen in the antiphospholipid syndrome. A systematic study of the role of β2GPI in thrombus formation in vivo has not been performed to date. Herein, we report that β2GPI deficient (-/-) mice have enhanced thrombus formation compared to wild type (WT) mice in a laser-induced arteriole and venule model of thrombosis. Furthermore, neutrophil accumulation and elastase activity was enhanced in thrombi of β2GPI -/- compared with WT mice. The antithrombotic function of β2GPI is dependent on its fifth domain (domain V); intravenous administration of the β2GPI domain deletion mutant lacking domain V (human recombinant domain I-IV) had no effect on platelet and fibrin thrombus size in β2GPI -/- or WT mice. On the contrary, intravenous administration of human recombinant domain V significantly inhibited platelet and fibrin thrombus size in both β2GPI -/- mice and WT mice. These findings reveal a major role for β2GPI as a natural anticoagulant and implicate domain V of β2GPI as a potential antithrombotic therapy.
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Affiliation(s)
- Freda H Passam
- Faculty Medicine Health, University of Sydney, Sydney, Australia; Heart Research Institute, Sydney, Australia
| | - Gang Chen
- Department of Infectious Disease, Immunology and Sexual Health, St George Hospital, University of New South Wales, Sydney, Australia
| | - Vivien M Chen
- Department of Haematology, Concord Hospital, Sydney, NSW, Australia; ANZAC Research Institute, University of Sydney, NSW, Australia
| | - Miao Qi
- Department of Infectious Disease, Immunology and Sexual Health, St George Hospital, University of New South Wales, Sydney, Australia
| | - Steven A Krilis
- Department of Infectious Disease, Immunology and Sexual Health, St George Hospital, University of New South Wales, Sydney, Australia; Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia.
| | - Bill Giannakopoulos
- Department of Infectious Disease, Immunology and Sexual Health, St George Hospital, University of New South Wales, Sydney, Australia; Department of Medicine, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia.
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2
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Wang X, Zhu X, Zhou H, Xia L, Wang T, Wang Z, Li Y, Yan J, Wang T. Anti-β 2GPI antibodies enhance atherosclerosis in ApoE-deficient mice. Biochem Biophys Res Commun 2019; 512:72-78. [PMID: 30871774 DOI: 10.1016/j.bbrc.2019.03.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 03/03/2019] [Indexed: 12/28/2022]
Abstract
Accelerated atherosclerosis often occurs in patients with antiphospholipid syndrome (APS), and auto-antibodies to β2 glycoprotein I (anti-β2GPI) are confirmed as pathogenic antibodies to APS. Our previous studies have demonstrated that the conversion of mouse peritoneal macrophages into foam cells could be enhanced by co-existence of β2GPI and anti-β2GPI IgG, but this phenomenon has not been explored in vivo. Here, we present a mouse model to observe the effect of anti-β2GPI IgG in the development of atherosclerosis. Male ApoE-deficient mice were intraperitoneally injected with anti-β2GPI IgG (100 μg/mouse) and homologous control IgG (100 μg/mouse) every week for 16 weeks. Plasma lipid composition, magnetic resonance imaging (MRI) and histological staining were used to evaluate vascular inflammation, lumen stenosis and plaque stability. The results showed that the levels of total cholesterol, triglycerol and low-density lipoprotein-cholesterol in plasma were not changed in all mice fed with high-fat diet, but the level of high-density lipoprotein-cholesterol was lower and the atherosclerosis index was significantly increased in HD + anti-β2GPI group than in other high-fat diet groups. In addition, compared with NR IgG-treated mice, anti-β2GPI IgG-treated mice showed more lipid deposition in the carotid artery, markedly narrowed arteriolar lumen as well as higher MMP-9 expression, more macrophages and fewer collagen fibers in the aortic arch root. Furthermore, the aortic mRNA levels of TNF-α, IL-1β, and MCP-1 were significantly increased in anti-β2GPI IgG-treated mice. Together, these data indicate that anti-β2GPI IgG increases vascular inflammation, aggravates atherosclerosis and promotes the formation of vulnerable plaque in ApoE-deficient mice.
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Affiliation(s)
- Xiaoyan Wang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China; Department of Clinical Laboratory, Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213000, PR China
| | - Xiang Zhu
- Department of Cardiovascularology, Renji Hospital, Zhenjiang, Jiangsu, 212009, PR China
| | - Hong Zhou
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China.
| | - Longfei Xia
- Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China
| | - Ting Wang
- Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China
| | - Zhongqun Wang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China
| | - Yuefeng Li
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China
| | - Jinchuan Yan
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China.
| | - Ting Wang
- Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, PR China
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3
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Jacquot C, Wool GD, Kogan SC. Dilute Russell viper venom time interpretation and clinical correlation: A two‐year retrospective institutional review. Int J Lab Hematol 2018; 41:80-86. [DOI: 10.1111/ijlh.12925] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 07/26/2018] [Accepted: 08/08/2018] [Indexed: 10/28/2022]
Affiliation(s)
- Cyril Jacquot
- Divisions of Laboratory Medicine and Hematology Children's National Health System Washington District of Columbia
- Departments of Pediatrics and Pathology George Washington University School of Medicine and Health Sciences Washington District of Columbia
| | | | - Scott C. Kogan
- Department of Laboratory Medicine University of California San Francisco California
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4
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Gracia-Tello B, Isenberg D. Kidney disease in primary anti-phospholipid antibody syndrome. Rheumatology (Oxford) 2017; 56:1069-1080. [PMID: 27550302 DOI: 10.1093/rheumatology/kew307] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Indexed: 12/19/2022] Open
Abstract
APS is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for aPL. APS can be isolated (primary APS) or associated with other autoimmune diseases. The kidney is a major target organ in APS, and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal vasculature and renal veins). Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal involvement in patients with definite APS is treated with long-term anticoagulants as warfarin, but new treatments are being tried. The aim of this article is to review the links between primary APS and kidney disease.
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Affiliation(s)
| | - David Isenberg
- Centre for Rheumatology, University College London Hospitals, London, UK
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5
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Bai A. β2-glycoprotein I and its antibodies involve in the pathogenesis of the antiphospholipid syndrome. Immunol Lett 2017; 186:15-19. [DOI: 10.1016/j.imlet.2017.03.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 03/05/2017] [Accepted: 03/23/2017] [Indexed: 11/26/2022]
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Gkogkolou P, Ehrchen J, Goerge T. Severe antiphospholipid antibody syndrome - response to plasmapheresis and rituximab. J DERMATOL TREAT 2017; 28:564-566. [PMID: 28084106 DOI: 10.1080/09546634.2017.1282599] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by arterial and/or venous thrombosis, recurrent abortions and detection of antiphospholipid antibodies. In fulminant cases, involvement of multiple organs can lead to significant morbidity and even fatal outcomes, so that a rapid, interdisciplinary treatment is needed. Here, we describe the case of a 39-year-old woman with a severe hard-to-treat APS with arterial occlusion and progressive skin necrosis, who was successfully treated with a combination therapy with plasmapheresis and rituximab. The treatment led to complete remission of the skin lesions for over a year. Clinical response correlated with a long-lasting reduction of antiphospholipid antibodies and B-cell depletion. This case demonstrates the use of antiphospholipid antibodies for monitoring APS-activity and shows that this severe vascular disease requires rigorous therapeutic approaches.
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Affiliation(s)
- Paraskevi Gkogkolou
- a Department of Dermatology , University Hospital of Münster , Münster , Germany
| | - Jan Ehrchen
- a Department of Dermatology , University Hospital of Münster , Münster , Germany
| | - Tobias Goerge
- a Department of Dermatology , University Hospital of Münster , Münster , Germany
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Abstract
Venous thromboembolism, usually entailing deep vein thrombosis, pulmonary embolism, or both, is a complex and multifactorial disorder, in which a number of putative conditions interplay and finally contribute to propel the individual risk over a certain degree, so ultimately culminating in the development of venous occlusive disorders. Thrombophilia is commonly defined as a propensity to develop venous thromboembolism on the basis of an underlying hypercoagulable state attributable to inherited or acquired disorders of blood coagulation or fibrinolysis. The thrombophilic conditions are conventionally classified as inherited (or genetically determined) and acquired. The former include deficiencies of natural anticoagulants such as antithrombin, protein C, protein S, increased values of clotting factors (especially factor VIII), as well as prothrombotic polymorphisms in genes encoding for factor V (i.e., factor V Leiden) and prothrombin. The latter conditions mainly entail antiphospholipid antibody syndrome, malignancy, acquired elevations of coagulation factors or acquired reduction of natural inhibitors, or hyperhomocysteinemia. Deepened knowledge of all potential risk factors, as well as the clear understanding of their role in the pathophysiology of venous thrombosis, are both essential to help achieve a faster and more efficient diagnosis of this condition as well as a more effective prophylaxis of patients at higher risk and treatment of those with manifest disease.
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Affiliation(s)
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
| | - Elisa Danese
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
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8
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Parajuli S, Lockridge JB, Langewisch ED, Norman DJ, Kujovich JL. Hypercoagulability in Kidney Transplant Recipients. Transplantation 2016; 100:719-726. [PMID: 26413991 DOI: 10.1097/tp.0000000000000887] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Thrombosis remains an important complication after kidney transplantation. Outcomes for graft and deep vein thrombosis are not favorable. The majority of early kidney transplant failure in adults is due to allograft thrombosis. Risk stratification, early diagnosis, and appropriate intervention are critical to the management of thrombotic complications of transplant. In patients with end-stage renal disease, the prevalence of acquired risk factors for thrombosis is significantly high. Because of hereditary and acquired risk factors, renal transplant recipients manifest features of a chronic prothrombotic state. Identification of hereditary thrombotic risk factors before transplantation may be a useful tool for selecting appropriate candidates for thrombosis prophylaxis immediately after transplantation. Short-term anticoagulation may be appropriate for all patients after kidney transplantation.
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Affiliation(s)
- Sandesh Parajuli
- 1 Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI. 2 Division of Nephrology, Department of Medicine, Oregon Health and Science University, Portland, OR. 3 Portland VA Medical Center, Portland, Oregon. 4 Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR
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9
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Xia L, Xie H, Yu Y, Zhou H, Wang T, Yan J. The Effects of NF-κB and c-Jun/AP-1 on the Expression of Prothrombotic and Proinflammatory Molecules Induced by Anti-β2GPI in Mouse. PLoS One 2016; 11:e0147958. [PMID: 26829121 PMCID: PMC4735462 DOI: 10.1371/journal.pone.0147958] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 01/10/2016] [Indexed: 01/07/2023] Open
Abstract
Our previous data demonstrated that nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are involved in the process of anti-β2GPI/β2GPI-induced tissue factor (TF) expression in monocytes. However, the role of NF-κB and AP-1 in pathogenic mechanisms of antiphospholipid syndrome (APS) in vivo has been rarely studied. This study aimed to investigate whether NF-κB and c-Jun/AP-1 are involved in anti-β2GPI-induced expression of prothrombotic and proinflammatory molecules in mouse. IgG-APS or anti-β2GPI antibodies were injected into BALB/c mice in the presence or absence of PDTC (a specific inhibitor of NF-κB) and Curcumin (a potent inhibitor of AP-1) treatment. Our data showed that both IgG-APS and anti-β2GPI could induce the activation of NF-κB and c-Jun/AP-1 in mouse peritoneal macrophages. The anti-β2GPI-induced TF activity in homogenates of carotid arteries and peritoneal macrophages from mice could significantly decrease after PDTC and/or Curcumin treatment, in which PDTC showed the strongest inhibitory effect, but combination of two inhibitors had no synergistic effect. Furthermore, anti-β2GPI-induced expression of TF, VCAM-1, ICAM-1 and E-selectin in the aorta and expression of TF, IL-1β, IL-6 and TNF-α in peritoneal macrophages of mice were also significantly attenuated by PDTC and/or Curcumin treatment. These results indicate that both NF-κB and c-Jun/AP-1 are involved in regulating anti-β2GPI-induced expression of prothrombotic and proinflammatory molecules in vivo. Inhibition of NF-κB and c-Jun/AP-1 pathways may be beneficial for the prevention and treatment of thrombosis and inflammation in patients with APS.
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Affiliation(s)
- Longfei Xia
- Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China
| | - Hongxiang Xie
- Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China
| | - Yinjing Yu
- Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China
| | - Hong Zhou
- Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
- * E-mail: (HZ); (JY)
| | - Ting Wang
- Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China
| | - Jinchuan Yan
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
- * E-mail: (HZ); (JY)
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10
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Yang A, Nayeemuddin M, Prasad B. Takayasu's arteritis and primary antiphospholipid syndrome presenting as hypertensive urgency. BMJ Case Rep 2016; 2016:bcr-2015-211752. [PMID: 26783006 DOI: 10.1136/bcr-2015-211752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 33-year-old Caucasian man was admitted to the hospital with chest pain and hypertensive urgency. Physical examination revealed widespread arterial bruits and marked difference in blood pressure between the upper limbs. Vascular imaging showed widespread narrowing in multiple vascular territories. He met the established American College of Rheumatology criteria for Takayasu's arteritis. His resistant hypertension was considered to be a consequence of bilateral renal artery stenosis and he subsequently underwent sequential stenting of his renal arteries leading to improvement in blood pressure and reduction in the number of antihypertensive medications. Subsequent imaging revealed progression of aortic thrombus in the setting of an elevated erythrocyte sedimentation rate, and persistently elevated antiphospholipid antibodies fulfilling diagnostic criteria for primary antiphospholipid syndrome, requiring initiation of immunosuppression and anticoagulation.
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Affiliation(s)
- Andrew Yang
- University of Saskatchewan, Regina, Saskatchewan, Canada
| | - Mohammed Nayeemuddin
- Department of Radiology, Regina Qu'Appelle Health Region, Regina, Saskatchewan, Canada
| | - Bhanu Prasad
- Department of Nephrology, Regina Qu'Appelle Health Region, Regina, Saskatchewan, Canada
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11
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Speth C, Rambach G, Würzner R, Lass-Flörl C, Kozarcanin H, Hamad OA, Nilsson B, Ekdahl KN. Complement and platelets: Mutual interference in the immune network. Mol Immunol 2015; 67:108-18. [DOI: 10.1016/j.molimm.2015.03.244] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 03/16/2015] [Accepted: 03/16/2015] [Indexed: 11/28/2022]
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12
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Xie H, Kong X, Zhou H, Xie Y, Sheng L, Wang T, Xia L, Yan J. TLR4 is involved in the pathogenic effects observed in a murine model of antiphospholipid syndrome. Clin Immunol 2015; 160:198-210. [PMID: 26065621 DOI: 10.1016/j.clim.2015.05.017] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 05/25/2015] [Accepted: 05/31/2015] [Indexed: 01/28/2023]
Abstract
Antiphospholipid (aPL)/anti-β2-glycoprotein I (β2GPI) antibodies are considered to play a pivotal pathogenic role in antiphospholipid syndrome (APS) by inducing an intracellular signaling and procoagulant/proinflammatory phenotype that leads to thrombosis. There is increasing evidence that Toll-like receptor 4 (TLR4) could serve as an important molecule for anti-β2GPI recognition on target cells. However, few studies have focused on the effects of TLR4 in in vivo models. Here, we investigated the role of TLR4 in the pathogenic effects of aPL/anti-β2GPI more precisely using TLR4-intact (C3H/HeN) and TLR4-defective (C3H/HeJ) mice. C3H/HeN and C3H/HeJ mice were injected with either IgG isolated from patient with APS (IgG-APS) or epitope-specific anti-β2GPI purified from β2GPI peptide-immunized rabbits. We found that, following anti-β2GPI injections and vascular injury, thrombus formation in both the carotid artery and femoral vein was markedly reduced in C3H/HeJ mice when compared with C3H/HeN mice. IgG-APS or anti-β2GPI-induced carotid artery and peritoneal macrophage tissue factor activity/expression was significantly lesser in C3H/HeJ than in C3H/HeN mice. Furthermore, the IgG-APS or anti-β2GPI induced expression of VCAM-1, ICAM-1, and E-selectin in the aorta and of IL-1β, IL-6, and TNF-α in peritoneal macrophages of C3H/HeJ mice was also significantly reduced compared to C3H/HeN mice. Together, these data suggest that TLR4 is involved in the pathogenic effects of aPL/anti-β2GPI antibodies in vivo.
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Affiliation(s)
- Hongxiang Xie
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Xiangmin Kong
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Hong Zhou
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
| | - Yachao Xie
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Liangju Sheng
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Medical Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Ting Wang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Longfei Xia
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Jinchuan Yan
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
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13
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HLA class II meets β2-glycoprotein I. Blood 2015; 125:2741. [PMID: 25931579 DOI: 10.1182/blood-2015-03-633644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Al-Bari MAA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother 2015; 70:1608-1621. [PMID: 25693996 PMCID: PMC7537707 DOI: 10.1093/jac/dkv018] [Citation(s) in RCA: 302] [Impact Index Per Article: 30.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Antimalarial drugs (e.g. chloroquine and its close structural analogues) were developed primarily to treat malaria; however, they are beneficial for many dermatological, immunological, rheumatological and severe infectious diseases, for which they are used mostly today. Chloroquine and hydroxychloroquine, two of the most fascinating drugs developed in the last 50 years, are increasingly recognized for their effectiveness in myriad non-malarial diseases. In advanced research, chloroquine and hydroxychloroquine have been shown to have various immunomodulatory and immunosuppressive effects, and currently have established roles in the management of rheumatic diseases, lupus erythematosus (different forms) and skin diseases, and in the treatment of different forms of cancer. Recently, chloroquine analogues have also been found to have metabolic, cardiovascular, antithrombotic and antineoplastic effects. This review is concerned with the lysosomotropic, anti-inflammatory and immunomodulatory mechanisms of chloroquine, hydroxychloroquine, quinacrine and related analogues, and the current evidence for both their beneficial effects and potential adverse manifestations in various diseases.
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Sun Y, Cui M, Zhu W, Xu W, Li N. A case report of a pregnancy-related death caused by primary antiphospholipid antibody syndrome. Int Med Case Rep J 2014; 7:159-63. [PMID: 25473318 PMCID: PMC4251530 DOI: 10.2147/imcrj.s71321] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Primary antiphospholipid antibody syndrome (APS) is a rare clinical event in the People’s Republic of China. As APS is easily neglected or misdiagnosed, a delayed treatment can result. The patient reported here was a 32-year-old female who died by systemic venous thrombosis on day 11 after a cesarean section delivery. Luckily, the baby survived. A blood test demonstrated that the patient’s platelets were decreased at 19 weeks of gestation. Anti-cardolipin antibody and antiβ2GP1 (anti-β2-glycoprotein-I antibody) were positive at 36 weeks and 2 days of gestation. This patient was diagnosed with APS. Unfortunately, as physicians, we could not provide proper treatment as the patient’s relatives were concerned that the proposed treatment would have negative effects on the infant’s health. This clinical case strongly suggests that physicians need to appreciate that APS is a very serious condition, especially for pregnant women, and that proper treatment should be provided as early as possible to avoid a bad outcome, despite the fact that a cure for this disease is not currently available.
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Affiliation(s)
- Yingjian Sun
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Manhua Cui
- Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Wanan Zhu
- Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Weiling Xu
- Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Na Li
- Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
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