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.
Department of Cell Chemistry, Department of Medicine III, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. eijimatu@md.okayama-u.ac.jp
Eiji
E
Matsuura
Kazuko
K
Kobayashi
Junko
J
Kasahara
Tatsuji
T
Yasuda
Hirofumi
H
Makino
Takao
T
Koike
Yehuda
Y
Shoenfeld
D001161:Arteriosclerosis / Q000209:etiology* / Q000276:immunology; D001323:Autoantibodies / Q000502:physiology*; D015551:Autoimmunity; D000939:Epitopes; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D010084:Oxidation-Reduction; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D000939:Epitopes; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein