Atherogenic autoantigen: oxidized LDL complexes with beta 2-glycoprotein I

E Matsuura, K Kobayashi, T Koike, Y Shoenfeld, M A Khamashta, G R V Hughes

Research output: Contribution to journalConference paper

26 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)17 - 22
Number of pages6
JournalImmunobiology
Volume207
Issue number1
Publication statusPublished - 2003
Event1st Tutzing Antiphospholipid Conference - TUTZING, Germany
Duration: 1 Jan 2003 → …

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