Mechanisms of autoantibody-mediated thrombosis.
It is widely hypothesized that autoantibodies directly contribute to the prothrombotic state in the antiphospholipid syndrome (APS). The discovery that antiphospholipid autoantibodies are specific for phospholipid-binding plasma proteins (beta2-glycoprotein I, prothrombin, etc.) has allowed a much more precise investigation of the interactions of autoantibodies and antigens, and the effects of these interaction on hemostasis. Recent studies suggest that two types of interactions may be important in the pathophysiology of APS: (1) antibody cross-linking of membrane bound antigens may alter the kinetics of phospholipid-dependent reactions; and (2) antibody cross-linking of antigens bound to cell surface receptors may trigger signal transduction and cellular activation. In light of these findings, previous reports implicating various mechanisms of autoantibody-mediated thrombosis are being re-evaluated.
Roubey
R A
RA
Division of Rheumatology & Immunology, University of North Carolina at Chapel Hill, 27599-7280, USA. roubey@med.unc.edu
D017153:Antibodies, Anticardiolipin / Q000276:immunology; D000937:Antigen-Antibody Reactions; D016736:Antiphospholipid Syndrome / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D002448:Cell Adhesion; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006487:Hemostasis; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000276:immunology; D008563:Membrane Lipids / Q000276:immunology; D018448:Models, Immunological; D009000:Monocytes / Q000378:metabolism; D010743:Phospholipids / Q000276:immunology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D019851:Thrombophilia / Q000276:immunology*; D013925:Thromboplastin / Q000502:physiology; D013927:Thrombosis / Q000209:etiology* / Q000276:immunology; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D008563:Membrane Lipids; D010743:Phospholipids; D017395:Plasminogen Activator Inhibitor 1; D053482:beta 2-Glycoprotein I; D013925:Thromboplastin