**3. The conventional concepts of antiphospholipid antibodies in APS**

APS is diagnosed both by the presence of clinical manifestations, including vascular thrombosis and pregnancy morbidity, and by the presence of antiphospholipid antibodies (aPLs) which present a laboratory criteria for APS [6]. Laboratory criteria for APS include IgG and IgM anticardiolipin antibodies (aCLs), IgG and IgM anti-β2-glycoprotein I (aβ2GPI) antibodies, and lupus anticoagulant (LAC). aPLs are thought to recognize linear β2-glycoprotein I (β2GPI), which undergoes conformational changes from the circular form of β2GPI by binding to negatively charged phospholipids [7], and cause APS by interacting with vascular endothelial cells [8]. Therefore, β2GPI bound to negatively charged phospholipids or negatively charged plates is used clinically to detect autoantibodies in APS patients [9]. However, because autoantibodies against the β2GPI complexed to negatively charged phospholipids or high binding plates are detected in less than half of patients with clinical manifestations of APS [10–12], these facts suggest that additional targets of autoantibodies may exist. Furthermore, because β2GPI is a secreted protein, it cannot be universally present on the cell surface. Therefore, there might be other specific molecules which present β2GPI on the surface of vascular endothelial cells.
