Conformation of beta2glycoprotein I and its effect on coagulation

Abstract

β2glycoprotein I (β2GPI) is the major antigen in the antiphospholipid syndrome. It has been shown that β2GPI can adapt to different conformations, a circular, a S-shaped and a J-shaped conformation. In literature anticoagulant properties of β2GPI have been indicated, though there is no consensus on how β2GPI exerts a certain action. This article will first review existing data on the conformation of β2GPI. In addition, we will investigate whether the conformation of β2GPI plays a role in in the proposed anticoagulant activity of β2GPI. We investigated the effect of native β2GPI and phospholipid-bound β2GPI on thrombin generation (TG). Native β2GPI was found to have no significant effect on the TG regardless of the concentration of tissue factor. On the contrary, β2GPI preincubated with phospholipids significantly inhibited TG triggered with low TF concentration, suggesting an effect on the intrinsic pathway. This indicates that native β2GPI in circulation obtains its anticoagulant activity in the presence of anionic phospholipids such as activated blood cells thereby serving as an inhibitory modulator in hemostasis.