Atherogenic autoantigen: oxidized LDL complexes with beta2-glycoprotein I.
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| Abstract |
Beta2-Glycoprotein I (beta2-GPI) is a major antigen for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). In 1997, we demonstrated that beta2-GPI specifically binds to Cu2+-oxidized low-density lipoprotein (oxLDL) and that the beta2-GPI-oxLDL complex is subsequently targeted by anti-beta2-GPI antibodies in vitro. Then ligands for beta2-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-beta2-GPI complexes, and the complexes are taken up avidly by macrophages via anti-beta2-GPI autoantibody-mediated phagocytosis. We recently demonstrated that appearance of autoantibodies against a complex of beta2-GPI and oxLig-1 are highly associated with a history of arterial thrombosis. Serum oxLDL-beta2-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 beta2-GPI and oxLDL in the atherogenesis in APS.
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| Authors | Eiji Matsuura, Kazuko Kobayashia, Takao Koikeb, Yehuda Shoenfeld, Munther A Khamashta, Graham R V Hughes |
| Journal | Immunobiology (Immunobiology) Vol. 207 Issue 1 Pg. 17-22 ( 2003) ISSN: 0171-2985 [Print] Netherlands |
| PMID | 12638898 (Publication Type: Journal Article, Review) |
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