Oxidized LDL/β₂-glycoprotein I complexes: New aspects in atherosclerosis

β₂-glycoprotein I (β₂GPI) is a major antigenic target for antiphospholipid antibodies. Oxidized low-density lipoprotein (oxLDL) is the principal lipoprotein found in atherosclerotic lesions, and it colocalizes with β₂GPI and immunoreactive lymphocytes. oxLDL/β₂GPI complexes appeared in the blood circulation of patients with diseases, such as systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis, diabetes mellitus and chronic renal diseases. Thus, the complexes may be associated with systemic and chronic inflammation of the vasculature. IgG anti- oxLDL/β₂GPI complexes autoantibodies and their immune complexes were detected only in SLE/APS patients and in its animal model and were strongly associated with arterial thrombosis. The oxLDL/β₂GPI complexes were internalized by macrophages via IgG anti-β₂GPI antibody-mediated phagocytosis. In contrast, IgM anti-oxLDL antibodies derived from hyperlipidemic mice reduced the incidence of atherosclerosis. The distribution patterns of IgG and IgM anti-oxLDL antibodies in patients suggest the different roles of these antibodies.