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Atherogenic Oxidized Low-Density Lipoprotein/ß2-Glycoprotein I (oxLDL/ß2GPI) Complexes in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome

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

K Kobayashi

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

BL Hurley

Corgenix, Inc., Westminster, Colorado, USA

LR Lopez

Corgenix, Inc., Westminster, Colorado, USA

Oxidized low-density lipoprotein (oxLDL) interacts in vitro with ß ₂-glycoprotein I (ß ₂GPI) via LDL-derived specific ligands forming oxLDL/ß ₂GPI complexes. Circulating oxLDL/ß ₂GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Autoimmune vascular inflammation and oxidative stress contribute to oxLDL/ß ₂GPI complex formation. Immunohistochemical staining of atherosclerotic lesions suggest that these complexes are formed in the arterial wall and released into circulation. The demonstration of antibodies to oxLDL/ß ₂GPI complexes indicates that these complexes are immunogenic, and the coexistence of complexes and antibodies suggest an active pro-thrombotic/pro-atherogenic role in the development of autoimmune vascular complications. Circulating oxLDL/ß ₂GPI complexes can be measured by ELISA using a monoclonal antibody specific to complexed human ß ₂GPI to capture ß ₂GPI bound to oxLDL. An enzyme-conjugated monoclonal antibody to human Apo B 100 allows the specific detection of oxLDL/ß ₂GPI complexes. OxLDL/ß ₂GPI complexes were common in SLE and APS patients suggesting an underlying process of inflammation and oxidation. Using oxLDL/ß ₂GPI complexes as capture antigen, antibodies to oxLDL/ß ₂GPI can be measured by ELISA. Serum levels of IgG anti-oxLDL/ß ₂GPI antibodies were significantly higher in SLE patients with APS compared to SLE controls without APS. Further, high titers of these IgG antibodies were observed in APS patients with a history of arterial thrombosis. The presence of circulating oxLDL/ß ₂GPI complexes and IgG antibodies to these complexes indicates significant vascular injury and oxidative stress as well as an active role in autoimmune-mediated atherothrombosis.

Key Words: antiphospholipid antibodies • autoimmunity • oxidized-LDL antibodies

Lupus, Vol. 15, No. 7, 478-483 (2006)
DOI: 10.1191/0961203306lu2337oa


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