Linking clotting and autoimmunity.

Abstract

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by increased risk for arterial, venous and/or microvascular thrombosis and various obstetrical complications, including recurrent miscarriages, premature births, and preeclampsia, in association with the persistent presence of phospholipid antibodies (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 autoantibodies targeting cardiolipins and/or the plasma protein β-2-glycoprotein I (β2GPI). However, the full spectrum of specific autoantigens primarily recognized by aPLs remain unknown, which has hampered therapeutic development. On page XXX of this issue, Muller-Calleja <i>et al.</i> (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.