The significance of autoantibodies against β2-glycoprotein I

Groot, Philip G. de; Urbanus, Rolf T.

doi:10.1182/blood-2012-03-378646

Cited by 132 publications

(117 citation statements)

References 112 publications

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“…In these patients, most of the pro-thrombotic antiphospholipid antibodies are directed to the lipid-binding plasma protein β 2 glycoprotein I (β 2 GPI) or to β 2 GPI/phospholipid complexes, rather than to phospholipids alone (3,4). The primary serological criteria to classify APS includes the demonstration of IgG or IgM β 2 GPI-dependent anti-cardiolipin (aCL) and/or IgG or IgM anti-β 2 GPI antibodies detected by solid-phase immunoassays (5).…”

Section: Introductionmentioning

confidence: 99%

Differential assay reactivity of immunglobulin A anti-ß2 glycoprotein I antibodies: implications for the clinical interpretation of antiphospholipid antibody testing

Hood¹,

Snyder²,

Buckner³

et al. 2015

Eur J Rheumatol

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Objective: The routine measurement of IgA anticardiolipin (aCL) and IgA anti-β 2 glycoprotein I (anti-β 2 GPI) antibodies remain controversial despite several studies demonstrating an association with thromboembolic disease in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). This controversy may be a contributing factor for the current under use of IgA antiphospholipid antibodies. We aimed to investigate the nature of discrepant IgA anti-β 2 GPI reactivity to help define the diagnostic value of IgA antiphospholipid antibodies.Material and Methods: Four sera selected from SLE/APS patients and positive for antiphospholipid antibodies but having discrepant IgA anti-β 2 GPI reactivity on two commercial assays were studied. IgA antibodies were affinity purified to investigate anti-β 2 GPI reactivity. Column wash through and eluent fractions were tested on both IgA anti-β 2 GPI assays. Results were normalized to total protein. Assay conjugates and standards from the discrepant assays were interchanged.

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Section: Introductionmentioning

confidence: 99%

Differential assay reactivity of immunglobulin A anti-ß2 glycoprotein I antibodies: implications for the clinical interpretation of antiphospholipid antibody testing

Hood¹,

Snyder²,

Buckner³

et al. 2015

Eur J Rheumatol

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“…: protein C) leads to thrombosis [6]. Though, according to the widely accepted pathogenic model, it is believed that the autoantibodies directed against phospholipids are not pathogenic [9], current research reveals evidence for the pathogenic role of cofactor independent aPL and that the clinical studies do not support a dominant pathogenic role for antib 2 GPI antibodies [10].…”

Section: Pathogenesismentioning

confidence: 99%

The Laboratory Diagnosis of the Antiphospholipid Syndrome

Ahluwalia

Sreedharanunni

2016

Indian J Hematol Blood Transfus

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The Antiphospholipid Syndrome (APS) is classified based on the presence of both clinical and laboratory criteria. Both sets of criteria are subject to much review and intense research as it is becoming increasingly clear that no single test is specific for defining this autoimmune disorder. A number of leading international bodies have released guidelines in an attempt to improve the laboratory testing and reporting. The current review is an appraisal of some of the literature pertaining to the laboratory testing.

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“…[1][2][3] These antibodies, including anti-b2-glycoprotein-1 (anti-b2GP1) autoantibodies, recognize plasma proteins that bind to anionic phospholipids, among which b2GP1 is the major target. 4 Antibodies directed against b2GPI 5,6 are associated with thrombotic events in APS.…”

Section: Introductionmentioning

confidence: 99%

“…To amplify initial thrombus formation, aPL have to (1) bind to target cells; (2) activate those cells; and (3) facilitate intercellular and intermolecular interactions required for thrombus development. To identify the cell against which the anti-b2GP1 autoantibody/b2GP1 complexes in vivo is directed, we examined anti-b2GP1 autoantibody and b2GP1 binding to the vessel wall in a mouse after injury using intravital microscopy.…”

Section: Introductionmentioning

confidence: 99%

Platelets are required for enhanced activation of the endothelium and fibrinogen in a mouse thrombosis model of APS

Proulle

Furie

Merrill-Skoloff

et al. 2014

Blood

106

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• The anti-b2GP1 autoantibody/ b2GP1 complex binds to the platelet thrombus, amplifying platelet activation.• Platelets are required for enhanced activation of the endothelium and fibrin generation by the anti-b2GP1 autoantibody/b2GP1 complex.Antiphospholipid syndrome (APS) is defined by thrombosis, fetal loss, and the presence of antiphospholipid antibodies, including anti-b2-glycoprotein-1 autoantibodies (antib2GP1) that have a direct role in the pathogenesis of thrombosis in vivo. The cellular targets of the anti-b2GP1 autoantibody/b2GP1 complex in vivo were studied using a laserinduced thrombosis model of APS in a live mouse and human anti-b2GP1 autoantibodies affinity-purified from APS patients. Cell binding of fluorescently labeled b2GP1 and antib2GP1 autoantibodies revealed their colocalization on the platelet thrombus but not the endothelium. Anti-b2GP1 autoantibodies enhanced platelet activation, monitored by calcium mobilization, and endothelial activation, monitored by intercellular adhesion molecule-1 expression. When eptifibatide was infused to block platelet thrombus formation, enhanced fibrin generation and endothelial cell activation were eliminated. Thus, the anti-b2GP1 autoantibody/b2GP1 complex binds to the thrombus, enhancing platelet activation, and platelet secretion leads to enhanced endothelium activation and fibrin generation. These results lead to a paradigm shift away from the concept that binding of the anti-b2GP1 autoantibody/b2GP1 complex activates both endothelial cells and platelets toward one in which activation of platelets in response to anti-b2GP1 autoantibody/b2GP1 complex binding leads to subsequent enhanced endothelium activation and fibrin generation. (Blood. 2014;124(4):611-622) IntroductionAntiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or pregnancy morbidity and is associated with circulating antiphospholipid (aPL) autoantibodies.1-3 These antibodies, including anti-b2-glycoprotein-1 (anti-b2GP1) autoantibodies, recognize plasma proteins that bind to anionic phospholipids, among which b2GP1 is the major target. 4 Antibodies directed against b2GPI 5,6 are associated with thrombotic events in APS. Antib2GP1 autoantibodies from patients with APS and thrombosis enhance arterial thrombus formation after injury in a mouse model of APS, 7 with dramatic increases in platelet thrombus size and fibrin generation.The mechanisms leading to thrombosis in APS are unresolved. In vitro and in vivo studies using animal models demonstrated that aPL antibodies interact with endothelial cells and monocytes to increase tissue factor expression and complement activation and proinflammatory cytokines. 8,9 In vitro, platelet activation occurs after the binding of complexes of anti-b2GP1 antibodies and dimerized b2GP1 to GPIba and ApoER2. [10][11][12] Furthermore, APS patients exhibit markers of platelet activation. 13 The conventional understanding is that the antib2GP1/b2GP1 complex binds to receptors on both the endothelial cell and the platelet, lea...

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The significance of autoantibodies against β2-glycoprotein I

Cited by 132 publications

References 112 publications

Differential assay reactivity of immunglobulin A anti-ß2 glycoprotein I antibodies: implications for the clinical interpretation of antiphospholipid antibody testing

Differential assay reactivity of immunglobulin A anti-ß2 glycoprotein I antibodies: implications for the clinical interpretation of antiphospholipid antibody testing

The Laboratory Diagnosis of the Antiphospholipid Syndrome

Platelets are required for enhanced activation of the endothelium and fibrinogen in a mouse thrombosis model of APS

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