antiphospholipid syndrome Autoantibodies against the fibrinolytic receptor, annexin 2, in

Abstract The association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and beta-2-glycoprotein-I, the main antigen for antiphospholipid antibodies. Here we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with non-autoimmune thrombosis, and 145 healthy individuals) were analyzed by ELISA and immunoblot for antiphospholipid and A2 antibodies (anti-A2Ab). Anti-A2Ab (titer >3SD) were significantly more prevalent in patients with APS (22.6%, venous 17.5%, arterial 34.3% and mixed thrombosis 40.4%), than in healthy individuals (2.1%, p<0.001), patients with non-autoimmune thrombosis (0%, p=0.017) or patients with lupus without thrombosis (6.3%, p<0.001). Anti-A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4 fold ± 0.13 SE), blocked A2-supported plasmin generation in a tPA-dependent generation assay (19 –71%) independently of beta-2-glycoprotein-I, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECS) by 34-83%. We propose that anti-A2Ab contribute to the prothrombotic diathesis in antiphospholipid syndrome.