Atherosclerosis and the antiphospholipid syndrome: A link unravelled?

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 140-143 ◽  
Author(s):  
Y Shoenfeld ◽  
D Harats ◽  
J George
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Dominant Role ◽  
Clinical Manifestations ◽  
Humoral Response ◽  
Arterial System ◽  
Glycoprotein I ◽  
Shock Proteins ◽  
Modified Forms ◽  
Progression Of Atherosclerosis

Atherosclerosis is a multifactorial disease that involves the arterial system. Recent data suggest that immune and autoimmune factors play a dominant role in mediating the progression of atherosclerosis. Among these factors, humoral response to modified forms of LDL and heat-shock proteins has been shown to be influential. The antiphospholipid syndrome (APS) entails clinical manifestations that result from a hypercoagulable state. Antibodies to phospholipids and to β2-glycoprotein I have been suggested to confer the tendency to thrombosis. In a set of recent studies, we have been able to show that generation of antiphospholipid antibodies in mice is associated with enhanced atherosclerosis. These findings imply that APS and atherosclerosis may share a common etiologic background, which may have direct implications for the management of both conditions.

scholarly journals Isolated IgA Anti-β2 Glycoprotein I Antibodies in Patients with Clinical Criteria for Antiphospholipid Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Raquel Ruiz-García ◽  
Manuel Serrano ◽  
José Ángel Martínez-Flores ◽  
Sergio Mora ◽  
Luis Morillas ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Clinical Manifestations ◽  
Diagnostic Systems ◽  
Clinical Criteria ◽  
Glycoprotein I ◽  
Standardized Diagnostic ◽  
Disease Present

Seronegative antiphospholipid syndrome (SNAPS) is an autoimmune disease present in patients with clinical manifestations highly suggestive of Antiphospholipid Syndrome (APS) but with persistently negative consensus antiphospholipid antibodies (a-PL). IgA anti-β2 Glycoprotein I (aB2-GPI) antibodies are associated with APS. However, they are not currently considered to be laboratory criteria due to the heterogeneity of published works and the use of poor standardized diagnostic systems. We have aimed to assess aPL antibodies in a group of patients with clinical manifestations of APS (C-APS) to evaluate the importance of the presence of IgA aB2GPI antibodies in APS and its relation with other aPL antibodies. Only 14% of patients with C-APS were positive for any consensus antibody, whereas the presence of isolated IgA aB2GPI antibodies was found in 22% of C-APS patients. In patients with arterial thrombosis IgA aB2GPI, antibodies were the only aPL antibodies present. Serologic profile in primary APS (PAPS) is different from systemic autoimmune disorders associated APS (SAD-APS). IgA aB2GPI antibodies are more prevalent in PAPS and IgG aB2GPI antibodies are predominant in SAD-APS. The analysis of IgA aB2GPI antibodies in patients with clinical manifestations of PAPS might avoid underdiagnosed patients and provide a better diagnosis in patients with SAD-APS. Laboratory consensus criteria might consider including analysis of IgA aB2GPI for APS diagnosis.

Non β2-Glycoprotein I Cofactors for Antiphospholipid Antibodies

Lupus ◽  
1996 ◽  
Vol 5 (5) ◽  
pp. 388-392 ◽  
Author(s):  
M Galli
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Protein C ◽  
Activated Protein C ◽  
Clinical Manifestations ◽  
Annexin V ◽  
Protein S ◽  
Thromboembolic Events ◽  
Glycoprotein I ◽  
Recurrent Abortions

The Antiphospholipid Syndrome is defined by the association between peculiar clinical manifestations, namely arterial and/or venous thrombosis, recurrent abortions and thrombocytopenia, and the antiphospholipid antibodies. These antibodies are directed to plasma proteins bound to anionic phospholipids or other anionic surfaces: so far, β2-glycoprotein I is the best known and characterized antiphospholipid ‘cofactor’ ( this issue is specifically treated in other parts of this journal). In recent years, such a role has been reported also for prothrombin, activated Protein C, Protein S, Annexin V, Thrombomodulin, high- and low-molecular weight kininogens. Anti-prothrombin antibodies are detected in approximately 50% of the antiphospholipid-positive patients; conversely, limited data are available regarding the prevalence the other antibodies. ‘Cofactors' are necessary for the expression of both the immunological and the functional properties of their respective antiphospholipid antibodies. In particular, the recognition of the calcium-mediated prothrombin/lipid complex by anti-prothrombin antibodies hampers prothrombin activation, thus causing the prolongation of the phospholipid-dependent coagulation reactions. The interaction between antiphospholipid antibodies and natural inhibitors of coagulation such as activated Protein C, its non-enzymatic accessory protein Protein S or Thrombomodulin might increase the risk to develop thromboembolic events. Similarly, the presence of antibodies to surface-bound Annexin V has been hypothesized to play a role in recurrent abortions and fetal deaths. However, to clearly establish whether and which antiphospholipid antibodies represent risk factors for the thromboembolic events of the antiphospholipid syndrome, further studies of their behaviour and properties as well as the identification and characterization of (possibly) other antibodies are required.

Current concepts on the pathogenesis of the antiphospholipid syndrome

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 422-430 ◽  
Author(s):  
Bill Giannakopoulos ◽  
Freda Passam ◽  
Soheila Rahgozar ◽  
Steven A. Krilis
Keyword(s):  
Experimental Evidence ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Peripheral Tolerance ◽  
The Core ◽  
Glycoprotein I ◽  
Antigenic Targets ◽  
Acquired Thrombophilia

Abstract The antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia. It is characterized by the core clinical manifestations of thrombosis, either venous or arterial, and in women it can also be associated with recurrent fetal loss. The detection of persistently elevated levels of antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the diagnosis to be made. The dominant antigenic targets in APS are beta 2-glycoprotein I (β2-GPI) and prothrombin. There is an accumulating body of experimental evidence that suggests that specific subgroups of aPL Abs may directly contribute to disease pathogenesis. This review critically examines the experimental evidence underlying the various propositions made to explain how these antibodies may predispose to disease in humans. Furthermore, it also examines the evidence relating to the immunologic mechanisms that may contribute to the breakage of peripheral tolerance in this disorder. Delineating the strengths and limitations of the experimental evidence accumulated thus far will hopefully stimulate further experimentation toward achieving the ultimate goal of precisely defining the dominant pathogenic mechanisms operational in APS. This may pave the way for the development of improved therapies.

scholarly journals Challenges in the Diagnosis of the Antiphospholipid Syndrome

2010 ◽  
Vol 56 (6) ◽  
pp. 930-940 ◽  
Author(s):  
Katrien Devreese ◽  
Marc F Hoylaerts
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Complex Disease ◽  
Clinical Manifestations ◽  
Clinical Role ◽  
Clinical Criteria ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Coagulation Tests

Abstract Background: The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. Its diagnosis is based on clinical and laboratory criteria, defined by strict guidelines. The original clinical and laboratory criteria for the identification of APS patients were published in 1999, in the so-called Sapporo criteria. In 2006 these criteria were revised, and recently more precise guidelines for analysis of the lupus anticoagulant have been provided. However, several questions related to the diagnosis of APS remain unanswered. Content: In addition to providing a historical perspective, this review covers several challenges in the diagnosis of APS with respect to clinical and laboratory features, while highlighting pathogenic pathways of the syndrome. We discuss ongoing dilemmas in the diagnosis of this complex disease. Although antiphospholipid antibodies are found in association with various clinical manifestations, the older established clinical criteria were not substantively altered in the 2006 update. Several laboratory tests recommended in the latest criteria, including phospholipid-dependent coagulation tests for the detection of the lupus anticoagulant and ELISAs for measuring anticardiolipin and β2-glycoprotein I antibodies, still show methodological and diagnostic shortcomings. In addition, antiphospholipid antibodies have been described against other antigens, but their clinical role remains uncertain. Conclusions: Despite updated APS criteria, diagnosis of this syndrome remains challenging. Further research on clinically relevant antibodies and standardization of their detection are needed to improve clinical risk assessment in APS.

scholarly journals Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gunay Uludag ◽  
Neil Onghanseng ◽  
Anh N. T. Tran ◽  
Muhammad Hassan ◽  
Muhammad Sohail Halim ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Autoimmune Disorder ◽  
Ocular Involvement ◽  
Ocular Manifestations ◽  
Different Types ◽  
Thrombotic Complications ◽  
Specific Factors ◽  
Arteries And Veins

AbstractAntiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

scholarly journals Anticardiolipin Antibodies in Patients with Chronic Hepatitis C Virus Infection: Characterization in Relation to Antiphospholipid Syndrome

2000 ◽  
Vol 7 (2) ◽  
pp. 241-244 ◽  
Author(s):  
Josep Ordi-Ros ◽  
Julieta Villarreal ◽  
Francesc Monegal ◽  
Silvia Sauleda ◽  
Ignacio Esteban ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Antiphospholipid Syndrome ◽  
Clinical Manifestations ◽  
Cross Reactivity ◽  
Healthy Controls ◽  
Glycoprotein I ◽  
Chronic Hepatitis C Virus

ABSTRACT The antiphospholipid syndrome (APS) is usually defined by the association of clinical manifestations that comprise venous and/or arterial thrombosis, recurrent fetal losses, and thrombocytopenia, along with the presence of anticardiolipin (aCL) antibodies and/or lupus anticoagulant. Various infectious diseases can induce aCL; however, these antibodies are not usually associated with thrombotic events, as happens with autoimmune diseases, in which these antibodies need the presence of β2-glycoprotein I. Levels of immunoglobulin G (IgG) and IgM aCL antibodies were determined by enzyme-linked immunosorbent assay for 243 patients with chronic hepatitis C virus (HCV) infection and 100 healthy controls. Clinical events of APS, the level of β2-glycoprotein dependence of aCL, the presence of cryoglobulins and other autoantibodies, and cross-reactivity between purified aCL and HCV were evaluated. Positive results for aCL antibodies were found more frequently (3.3%) for the patients with HCV infection than for healthy controls (0%). All positive aCL antibodies were β2-glycoprotein I independent. No significant association was found between aCL antibodies and clinical manifestations of APS, neither was one found between the presence of other autoantibodies or cryoglobulins and that of aCL. Finally, no cross-reactivity between aCL antibodies and HCV antigens was observed. As previously reported, aCL antibodies seem to be an epiphenomenon, and they do not have clinical or laboratory significance in HCV patients.

β2-Glycoprotein I: Target antigen for ‘antiphospholipid’ antibodies. Immunological and molecular aspects

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 5-9 ◽  
Author(s):  
Y Sheng ◽  
DA Kandiah ◽  
SA Krilis
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Fluid Phase ◽  
Target Antigen ◽  
Phospholipid Membranes ◽  
Anionic Phospholipid ◽  
Glycoprotein I ◽  
High Concentrations ◽  
Molecular Aspects ◽  
Anionic Phospholipid Membranes

It has become clear that β2-glycoprotein I (β2GPI) is the most common and best-characterised antigenic target for ‘antiphospholipid’ (aPL) autoantibodies. These antibodies preferentially bind β2GPI that has been immobilised on anionic phospholipid membranes or certain synthetic surfaces. These surfaces appear to act by increasing antigen density to allow binding of intrinsically low-affinity anti-β2GPI autoantibodies. Binding of β2GPI in fluid phase is weak and requires high concentrations of β2GPI. Our understanding of the pathophysiology of the ‘Antiphospholipid’ Syndrome (APS) has increased exponentially with the number of studies into the interactions of aPL antibodies and β2GPI.

Antibodies Against Platelet Glycoprotein Target Antigens in Antiphospholipid Syndrome (APS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3973-3973 ◽  
Author(s):  
Carlos J. Bidot ◽  
Wenche Jy ◽  
Carlos Bidot ◽  
Lawrence L. Horstman ◽  
Vincenzo Fontana ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Dominant Role ◽  
Endothelial Activation ◽  
Platelet Glycoprotein ◽  
Activation Markers ◽  
Positive Group ◽  
Platelet Antibodies ◽  
Platelet Microparticles

Abstract Introduction: Antiphospholipid syndrome (APS) is characterized clinically by thrombotic events and the presence of antiphospholipid antibodies (aPLA) and/or lupus anticoagulant (LA). It is frequently associated with thrombocytopenia and anti-platelet antibodies have been implicated by some. However the roles of anti-platelet antibodies in APS have not been elucidated. We previously reported that platelet activation, but not endothelial activation, was associated with thrombosis in aPLA+ patients [Blood, 104:143a, 2004] but the cause of platelet activation was not addressed. In the present study, we investigated the prevalence of anti-platelet antibodies in APS patients, as well as platelet and endothelial activation. Material and Methods: We evaluated 47 patients with primary APS. Anti-platelet antibodies against GP IIb/IIIa (CD41b), GP Ib/IX (CD 42b) and GP IV (CD36) for IgG and IgM class were measured by PAICA assay [Thromb Haemost76:1820, 1996]. We also measured platelet and endothelial activation markers by flow cytometry: CD62P on platelets, CD31+/CD42+ platelet microparticles (PMP), and CD31+/CD42- endothelial microparticles (EMP). Results: Of the 47 patients, 34 (72%) were positive for at least one anti-platelet antibody. Looking first at IgG, 18/34 (53%) were positive for GP IV; 17/34 (50%) for GP IIb/IIIa; and 16/34 (47%) for GP Ib/IX. IgM antibodies were 47% (14/30) for GP Ib/IX, 38%(13/34) for GP IIb/IIIa, and 24% (8/33) for GP IV. Platelet and endothelial markers were significantly more common in the anti-platelet antibodies positive group: 40% vs. 21% for CD62P, 40% vs. 28.5% for EMP, and 23% vs. 5% for PMP, respectively. We found that CD62P associated significantly with IgM anti-GP IIb/IIIa (p< 0.05), and PMP with IgM anti-GP IIb/IIIa (p< 0.05), and IgM anti-GP IV (p< 0.05). Conclusions: Anti-platelet antibodies are common in APS, confirming previous reports. We found that anti-platelet antibodies IgM anti-GP IIb/IIIa, and IgM anti-GP IV were often associated with platelet activation, suggesting that these antibodies may activate platelets to play an important role in the thrombogenesis of APS. These antibodies were also associated with endothelial activation. It remains to be determined which antibodies, APLA and/or anti-platelet antibodies, play a dominant role in the activation of platelet or endothelial cells and contibute most to the pathogenesis of thrombosis in APS.

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