Linking clotting and autoimmunity

Abstract

A receptor for phospholipid antibodies drives clotting and inflammation Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by increased risk for arterial, venous and/or microvascular thrombosis and various obstetric complications, including recurrent miscarriages, premature births, and preeclampsia, in association with the persistent presence of autoantibodies targeting phospholipids (aPLs). The clinical spectrum of APS ranges from mild clinical manifestations to the development of a catastrophic event involving multiorgan failure and high mortality due to disseminated thrombosis. APS diagnosis requires the detection of serum aPLs targeting cardiolipins and/or the plasma protein β2 glycoprotein I (β2GPI). However, the full spectrum of specific autoantigens primarily recognized by aPLs remains unknown, which has hampered therapeutic development. On page 1121 of this issue, Müller-Calleja et al. (1) report the identification of a cell surface antigenic complex composed of endosomal lysobiphosphatidic acid (LBPA) presented by the endothelial protein C receptor (EPCR), which is specifically recognized by aPLs and promotes immune dysregulation and thrombosis in mice.