Apoptosis and the antiphospholipid syndrome

The target of many antiphospholipid autoantibodies (APA) has been shown to be a complex between anionic phospholipid (PL) and the plasma protein beta 2-glycoprotein I (beta 2-GPI), but the identity of the natural target(s) an d/or immunogen for APA in vivo remains undetermined. The anionic PL of cell membranes represent important potential targets and immunogens for APA. Al though anionic PL are normally absent from the extracellular surface of cel l membranes, they redistribute from the inner to the outer leaflet during a poptosis. We and others have shown that beta 2-GPI binds selectively to the surface of apoptotic, but not viable, cells, and that the binding of beta 2-GPI to the surface of apoptotic cells generates an epitope recognized by APA from patients with both primary antiphospholipid syndrome (APS) and sys temic lupus erythematosus (SLE). In this review, we discuss recent findings , which suggest not only that apoptotic cell-bound beta 2-GPI induces the p roduction of APA, but that apoptotic cell-bound beta 2-GPI may be the actua l in vivo immunogen when heterologous beta 2-GPI is injected by non-intrave nous routes. We also review briefly the potential role of oxidation in gene rating epitopes responsible for the recognition and induction of APA. Taken together, we believe that the available evidence supports a role for apopt otic cells as targets of APA and possible players in the induction of APA. (C) 2000 Academic Press.