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

It has been shown that beta 2-glycoprotein I (beta 2GPI) 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 beta 2GPI might play a role in TTP. We found that beta 2GPI 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 beta 2GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of beta 2GPI to VWF by surface plasmon resonance, and determined that domain I of beta 2GPI is the binding site of VWF A1 domain. Adhesion of beta 2GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that beta 2GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that beta 2GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.