Anti-β2 glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via two receptors: apolipoprotein E receptor 2′ and glycoprotein I bα

Anti-β 2 glycoprotein I (anti-β 2 GPI ) antibodies are important contributors to thrombosis, especially in patients with antiphospholipid syndrome (APS). However, the mechanism by which anti-β 2 GPI antibodies are involved in the pathogenesis of thrombosis is not fully understood. In this report, we investigated the role of anti- β 2 GPI antibodies in complexes with β 2 GPI as mediators of platelet activation, which can serve as a potential source contributing to thrombosis. We examined the involvement of the apolipoprotein E receptor 2′ (apoER2′) and glycoprotein I ba (GP I ba) in platelet activation induced by the anti-β 2 GPI /β 2 GPI complex. The interaction between the anti-β 2 GPI /β 2 GPI complex and platelets was examined using in vitro methods, in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by measuring GPII b/III a activation and P-selectin expression and thromboxane B 2 production as well as p38 mitogen-activated protein kinase phosphorylation. Our results revealed that the anti-β 2 GPI /β 2 GPI complex was able to activate platelets, and this activation was inhibited by either the anti-GP I bα antibody or the apoER2′ inhibitor. Results showed that the anti-β 2 GPI /β 2 GPI complex induced platelet activation via GPI ba and apoER2′, which may then contribute to the prothrombotic tendency in APS patients.