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Oxidized LDL/ß2-glycoprotein I complexes: new aspects in atherosclerosis

Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan, eijimatu{at}md.okayama-u.ac.jp

K Kobayashi

Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

K Inoue

Department of Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, Japan

L R Lopez

Corgenix, Inc., Westminster, CO, USA

Y Shoenfeld

Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel, Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel-Aviv University, Tel-Aviv, Israel

ß₂-glycoprotein I (ß₂GPI) is a major antigenic target for antiphospholipid antibodies. Oxidized low-density lipoprotein (oxLDL) is the principal lipoprotein found in atherosclerotic lesions, and it colocalizes with ß₂GPI and immunoreactive lymphocytes. oxLDL/ß₂GPI complexes appeared in the blood circulation of patients with diseases, such as systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis, diabetes mellitus and chronic renal diseases. Thus, the complexes may be associated with systemic and chronic inflammation of the vasculature. IgG anti-oxLDL/ß₂GPI complexes autoantibodies and their immune complexes were detected only in SLE/APS patients and in its animal model and were strongly associated with arterial thrombosis. The oxLDL/ß₂GPI complexes were internalized by macrophages via IgG anti-ß₂GPI antibody-mediated phagocytosis. In contrast, IgM anti-oxLDL antibodies derived from hyperlipidemic mice reduced the incidence of atherosclerosis. The distribution patterns of IgG and IgM anti-oxLDL antibodies in patients suggest the different roles of these antibodies.

Key Words: antiphospholipid syndrome (APS) • atherosclerosis • autoantibody • ß2-glycoprotein I (ß2GPI) • oxidized low-density lipoprotein (oxLDL)

Lupus, Vol. 14, No. 9, 736-741 (2005)
DOI: 10.1191/0961203305lu2211oa


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