Anti-β 2 -Glycoprotein I Autoantibodies and Atherosclerosis

Abstract

β-Glycoprotein I (β 2 -GPI) is a major antigen for antiphospholipid antibodies (aPL) present in patients with antiphospholipid syndrome (APS). We previously reported that β 2 -GPI specifically binds to oxidized low-density lipoprotein (oxLDL). Further, a ligand specific for β 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-3β-yloxy) nonanoic acid) OxLig-1 was recognized by β 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 β 2 -GPI and an anti-β 2 -GPI autoantibody derived from (NZW×BXSB) F1 mouse, an animal APS model, or from APS patients. Anti-β 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 β 2 -GPI had an accelerated atherosclerosis and that β 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 β 2 -GPI interaction with oxLDL and autoantibodies may be present in APS.