Mechanisms of action of antiphospholipid antibodies

Antiphospholipid antibodies (aPL) are both diagnostic and pathogenic antibodies. aPL may: (1) interfere with anticoagulant mechanisms and fibrinolysis favoring a prothrombotic state, and (2) interact with cells of the coagulation cascade (i.e. endothelial cells, monocytes, and platelets) inducing a procoagulant phenotype. These pathogenic mechanisms have been reproduced in in vivo animal models. Thrombotic events explain in part the fetal losses associated with antiphospholipid syndrome (APS) and additional aPL-mediated mechanisms have been described that may contribute a defective placenta without placental thrombosis. A direct aPL interaction with kidney endothelial cells or with neuronal cells has been suggested to explain additional non-thrombotic manifestations of the syndrome, such as APS nephropathy and brain involvement with no clear signs of ischemic events. Finally, aPL have been shown to activate complement in both in vivo and in vitro experimental models. Whether or not such mechanisms play a role in APS patients is still a matter of research.