Induction of Anti-Phospholipid Autoantibodies by β2-glycoprotein I Bound to Apoptotic Thymocytes

摘要: Abstract The target of many anti-phospholipid autoantibodies (aPL) has been shown to be a complex between anionic phospholipid and the plasma protein β2-glycoprotein I (β2GPI) or β2GPI alone. As aPL binding studies have performed almost exclusively in vitrothe identity natural and/or immunogen for vivo remains undetermined. phospholipids cell membranes represent an important potential aPL. Although are normally absent from extracellular surface membranes, they redistribute inner outer leaflet during apoptosis. We previously that binds selectively apoptotic, but not viable, cells, apoptotic cells generates epitope recognized by patients with primary syndrome systemic lupus erythematosus. show here immunization non-autoimmune mice combined with, bound to, induces anticoagulant activity. Generation required heterologous β2GPI, occurred upon three different routes administration. Importantly, intravenous immuniz-ations, generation only when were injected together, either was alone, suggesting cell-bound is true production Unlike other models induced aPL, adjuvant absolute requirement. Induced reacted murine, as well bovine, can break tolerance induce auto-antibodies reactive autologous β2GPI. Combined our previous data, these results serve both immunogens targets