Atherogenic autoantigen: oxidized LDL complexes with beta2-glycoprotein I.
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.
Matsuura
Eiji
E
Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. eijimatu@md.okayama-u.ac.jp
Kobayashia
Kazuko
K
Koikeb
Takao
T
Shoenfeld
Yehuda
Y
Khamashta
Munther A
MA
Hughes
Graham R V
GR
D000818:Animals; D016736:Antiphospholipid Syndrome / Q000276:immunology; D001161:Arteriosclerosis / Q000517:prevention & control; D001324:Autoantigens / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism*; D008954:Models, Biological; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D012307:Risk Factors; D013927:Thrombosis / Q000150:complications; D053482:beta 2-Glycoprotein I
D001324:Autoantigens; D006023:Glycoproteins; D008024:Ligands; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein; D010100:Oxygen