[New insights into the pathogenicity of antiphospholipid antibodies].
Antiphospholipid antibodies (aPL) recognize phospholipid-binding proteins such as beta(2)-glycoprotein I (beta(2)-GPI) and prothrombin, inducing thrombosis and pregnancy morbidities. Pathogenicity of aPL has been established by many in vivo experiments in which administration of aPL resulted in pregnancy losses and/or thrombotic phenomena. The mechanisms how aPL cause such symptoms have been extensively investigated. aPL alters fibrinolysis/coagulation system by suppression of protein C/Z systems in the presence of beta(2)-GPI. B cell epitopes were also studied for specific therapies, resulting in diverse candidates such as domain I, IV or other domains. For T cells, importance of cryptic epitope on domain V was suggested. Recently, activation of endothelial cells, monocytes and thrombocytes by aPL with beta(2)-GPI has been reported. This activation is mainly mediated by p38MAP kinase activation and results in expression of tissue factor and adhesion molecules in endothelial cells and monocytes, thromboxane B2 in thrombocytes. Annexin II, toll-like receptor 4, LDL-receptor family members, and glycoprotein Ib are the candidates for cell surface ligands, suggesting the possibility of their blockades by monoclonal antibodies. Although treatment of APS is now limited to nonspecific anticoagulants or anti-platelet agents, based on these new insights, specific therapies targeting signal molecules and/or cell surface ligands for beta(2)-GPI should be introduced in near future.
Yasuda
Shinsuke
S
Department of Medicine II, Hokkaido University Graduate School of Medicine.
Koike
Takao
T
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000302:isolation & purification / Q000502:physiology*; D016736:Antiphospholipid Syndrome / Q000209:etiology*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011516:Prothrombin / Q000378:metabolism; D011697:Purpura, Thrombotic Thrombocytopenic / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D053482:beta 2-Glycoprotein I; D011516:Prothrombin