Anti-beta 2-glycoprotein I autoantibodies and atherosclerosis.

beta 2-Glycoprotein I (beta 2-GPI) is a major antigen for antiphospholipid antibodies (aPL) present in patients with antiphospholipid syndrome (APS). We previously reported that beta 2-GPI specifically binds to oxidized low-density lipoprotein (oxLDL). Further, a ligand specific for beta 2-GPI, oxLig-1, purified from the extracted lipids of oxLDL was identified as 7-ketocholesterol-9-carboxynonanoate (i.e., 9-oxo-9-(7-ketocholest-5-en-3 beta-yloxy) nonanoic acid) OxLig-1 was recognized by beta 2-GPI and subsequently by anti-beta 2-GPI autoantibodies. Binding of liposomes containing oxLig-1 to macrophages were significantly enhanced in the presence of both beta 2-GPI and an anti-beta 2-GPI autoantibody derived from (NZW x BXSB) F1 mouse, an animal APS model, or from APS patients. Anti-beta 2-GPI autoantibodies derived from APS patients with episodes of arterial thrombosis were detected in ELISA, using a solid phase beta 2-GPI complex with oxLig-1. It was also reported that LDL-receptor-deficient mice that were fed a chow diet and immunized with beta 2-GPI had an accelerated atherosclerosis and that beta 2-GPI was abundantly expressed within subendothelial regions and intimal-medial borders of human atherosclerotic plaques. All of these observations strongly suggest that autoimmune atherogenesis linked to beta 2-GPI interaction with oxLDL and autoantibodies may be present in APS.