Antiphospholipid antibodies and thrombosis.
Antiphospholipid antibodies are a diverse group of immunoglobulins initially thought to have specificity to phospholipid epitopes. It is apparent that autoimmune anticardiolipin antibodies require a serum cofactor beta-2-glycoprotein I (beta 2GPI) for their binding to phospholipids. Lupus anticoagulant also may bind to phospholipids by beta 2GPI or by prothrombin. The description of binding to protein-phospholipid epitopes may explain several perplexing features of these antibodies both in vitro and in vivo. Antiphospholipid antibodies have a well-established association with clinical disease--in particular thrombosis, thrombocytopenia and recurrent fetal loss. The mechanism of the predisposition to thrombosis seen with these antibodies is poorly understood. It has been suggested that they may cause endothelial dysfunction by causing increased tissue factor expression, by inhibiting prostacyclin secretion or by inhibiting fibrinolysis. Various platelet-activating activities have also been described. The evidence that antiphospholipid antibodies promote thrombosis by effects on endothelium or platelets is inconclusive. Inhibition of protein C activation, or of activated protein C action, has been demonstrated in vitro. A poor correlation between thrombosis in vivo and these inhibitory effects has been found. Beta-2-glycoprotein I has been identified as a cofactor for binding to phospholipid by thrombogenic anticardiolipin antibodies. That beta 2GPI may be a natural anticoagulant of importance remains to be proved. Inhibition by antiphospholipid antibodies of this anticoagulant function could explain the propensity to thrombosis seen in association with these antibodies.
Brighton
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TA
Centre for Thrombosis and Vascular Research, University of New South Wales, Prince of Wales Hospital, Randwick, Australia.
Chesterman
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CN
D017153:Antibodies, Anticardiolipin / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications*; D000990:Antithrombin III / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications*; D004730:Endothelium, Vascular / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005342:Fibrinolysis; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000276:immunology; D015539:Platelet Activation; D011486:Protein C / Q000276:immunology; D012306:Risk; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology* / Q000276:immunology; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D011486:Protein C; D053482:beta 2-Glycoprotein I; D000990:Antithrombin III; D013925:Thromboplastin; D011464:Epoprostenol