Atherogenic autoantigen: Oxidized LDL complexes with β2-glycoprotein I

β2-Glycoprotein I (β2-GPI) is a major antigen for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). In 1997, we demonstrated that β2-GPI specifically binds to CU²⁺-oxidized low-density lipoprotein (oxLDL) and that the β2-GPI-oxLDL complex is subsequently targeted by anti-β2-GPI antibodies in vitro. Then ligands for β2-GPI were purified from oxLDL and characterized as omega-carboxylated 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) dodecanoate (oxLig-2). These ligands mediate to form oxLDL-β2-GPI complexes, and the complexes are taken up avidly by macrophages via anti-β2-GPI autoantibody-mediated phagocytosis. We recently demonstrated that appearance of autoantibodies against a complex of β2-GPI and oxLig-1 are highly associated with a history of arterial thrombosis. Serum oxLDL-β2-GPI complex and their IgG immune complexes are also risk factors arterial thrombosis in APS patients. There is increasing circumstantial evidence of autoimmune mechanism involving β2-GPI and oxLDL in the atherogenesis in APS.