title: Atherogenic oxidized low-density lipoprotein/beta2-glycoprotein I (oxLDL/beta2GPI) complexes in patients with systemic lupus erythematosus and antiphospholipid syndrome.
abstract: Oxidized low-density lipoprotein (oxLDL) interacts in vitro with beta2-glycoprotein I (beta2GPI) via LDL-derived specific ligands forming oxLDL/beta2GPI complexes. Circulating oxLDL/beta2GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Autoimmune vascular inflammation and oxidative stress contribute to oxLDL/beta2GPI 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/beta2GPI 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/beta2GPI complexes can be measured by ELISA using a monoclonal antibody specific to complexed human beta2GPI to capture beta2GPI bound to oxLDL. An enzyme-conjugated monoclonal antibody to human Apo B 100 allows the specific detection of oxLDL/beta2GPI complexes. OxLDL/beta2GPI complexes were common in SLE and APS patients suggesting an underlying process of inflammation and oxidation. Using oxLDL/beta2GPI complexes as capture antigen, antibodies to oxLDL/beta2GPI can be measured by ELISA. Serum levels of IgG anti-oxLDL/beta2GPI 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/beta2GPI complexes and IgG antibodies to these complexes indicates significant vascular injury and oxidative stress as well as an active role in autoimmune-mediated atherothrombosis.
authors.affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. eijimatu@md.okayama-u.ac.jp
authors.forename: E
authors.initials: E
authors.lastname: Matsuura
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: B L
authors.initials: BL
authors.lastname: Hurley
authors.forename: L R
authors.initials: LR
authors.lastname: Lopez
mesh_terms: D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications; D008297:Male; D053482:beta 2-Glycoprotein I / Q000097:blood* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein