Oxidative post-translational modification of ßeta 2-glycoprotein I in the pathophysiology of the anti-phospholipid syndrome.

The anti-phospholipid syndrome (APS) is a prothrombotic autoimmune disorder characterized by either thrombosis or pregnancy complications in the setting of persistent anti-phospholipid antibodies (aPL). ßeta 2-glycoprotein I (ß2-GPI) is the major autoantigen in APS that binds anionic phospholipids as well as specific receptors on platelets and endothelial cells resulting in activation of prothrombotic pathways. ß2-GPI consists of 5 Domains that exist in a circular or linear form, with the latter occurring after binding to anionic phospholipids. ß2-GPI also undergoes dynamic posttranslational modification between oxidized and free thiol forms. The relationship between posttranslational modification and structural conformation is yet to be definitively clarified. Compared with controls, patients with the APS have higher levels of total ß2-GPI and lower levels of free thiol ß2-GPI. This raises the possibility of using quantification of ß2-GPI posttranslational modification as a redox biomarker in the management and diagnosis of the APS.