Annexin 2 Autoantibodies linked to antiphospholipid syndrome

Antiphospholipid syndrome (APS) related thrombosis is associated with autoantibodies against the fibrinolytic receptor annexin 2 (A2), according to new findings.Lead author Dr Gabriela Cesarman-Maus identifies A2 as a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and beta(2)-glycoprotein I (beta2GPI). This receptor however, is a major antigen for antiphospholipid antibodies. To determine if A2 antagonism contributes to the thromboembolic process the researchers studied serum samples from 434 subjects, (206 with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with non-autoimmune thrombosis, and 145 healthy individuals). Subjects were analysed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies.The group reports that A2 antibodies 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"Anti-A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold), blocked A2-supported plasmin generation in a tPA-dependent generation assay (19%) independently of beta2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%," writes Dr Cesarman-Maus's team.In an accompanying editorial, Dr Keith McCrae (Case Western Reserve University School of Medicine, Cleveland) comments, "annexin A2 must now be considered alongside annexin V as a potentially key component in the pathogenesis of APS."Referencec...