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Abstract

Oxidized low-density lipoprotein (oxLDL) interacts in vitro with β ₂-glycoprotein I (β ₂GPI) via LDL-derived specific ligands forming oxLDL/β ₂GPI complexes. Circulating oxLDL/β 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/β 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/β 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/β ₂GPI complexes can be measured by ELISA using a monoclonal antibody specific to complexed human β ₂GPI to capture β ₂GPI bound to oxLDL. An enzyme-conjugated monoclonal antibody to human Apo B 100 allows the specific detection of oxLDL/β ₂GPI complexes. OxLDL/β ₂GPI complexes were common in SLE and APS patients suggesting an underlying process of inflammation and oxidation. Using oxLDL/β ₂GPI complexes as capture antigen, antibodies to oxLDL/β ₂GPI can be measured by ELISA. Serum levels of IgG anti-oxLDL/β 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/β 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.

Keywords

antiphospholipid antibodies autoimmunity oxidized-LDL antibodies

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Atherogenic Oxidized Low-Density Lipoprotein/β2-Glycoprotein I (oxLDL/β2GPI) Complexes in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome

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