Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura

Abstract

It has been shown that β2-glycoprotein I (β2GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that β2GPI might play a role in TTP. We found that β2GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that β2GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of β2GPI to VWF by surface plasmon resonance, and determined that domain I of β2GPI is the binding site of VWF A1 domain. Adhesion of β2GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that β2GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that β2GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets. © 2012 Blackwell Publishing Ltd.