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Oxidized low-density lipoprotein and ß2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness: implications in autoimmune-mediated atherosclerosis

Corgenix, Inc., Westminster, Colorado, USA, llopez{at}corgenix.com

M Salazar-Paramo

Research Division, Hospital de Especialidades, CMNO, IMSS, Guadalajara, Mexico

C Palafox-Sanchez

Department of Immunology and Rheumatology, Hospital General de Occidente and Department of Physiology, CUCS, University of Guadalajara, Guadalajara, Mexico

B L Hurley

Corgenix, Inc., Westminster, Colorado, USA

E Matsuura

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

I Garcia-De La Torre

Department of Immunology and Rheumatology, Hospital General de Occidente and Department of Physiology, CUCS, University of Guadalajara, Guadalajara, Mexico

Oxidative stress and LDL modification (oxLDL) are early pro-atherogenic events. OxLDL binds ß2GPI producing immunogenic oxLDL/ß2GPI complexes. Antibodies to these complexes have been associated with arterial thrombosis in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Circulating oxLDL/ß2GPI complexes, IgG and IgM antibodies to these complexes were measured by ELISA in 30 SLE patients asymptomatic for cardiovascular disease (mean age 31 years) and 27 age/sex matched healthy controls. Carotid intima-media thickness (IMT) was measured by ultrasound in all patients and controls. Forty-seven percent of SLE presented plaques (median IMT of 0.65 ± 0.12 mm) while only 7% of the controls had plaques (median IMT of 0.50 ± 0.04 mm, P < 0.001). Median optical density (OD_450nm) for oxLDL/ß2GPI complexes in SLE was 0.244 ± 0.07, higher than controls (0.174 ± 0.09, P < 0.001). Median OD for IgG anti-oxLDL/ß2GPI antibodies was also higher in SLE (0.297 ± 0.26) compared to controls (0.194 ± 0.07, P < 0.001) while the median OD for IgM antibodies in SLE (0.444 ± 0.46) was not different than controls (0.326 ± 0.22, P = 0.267). There was no correlation between IMT and oxLDL/ß2GPI complexes, IgG or IgM antibodies, possibly reflecting the complex interrelationship between these serologic elements and tissue factors in the arterial wall. These results support the hypothesis that oxLDL/ß2GPI complexes and IgG (not IgM) anti-oxLDL/ß2GPI antibodies contribute to the development of autoimmune-mediated atherosclerosis

Key Words: autoimmune-mediated atherosclerosis • ß2-glycoprotein I • intima-media thickness • oxidized low-density lipoprotein • systemic lupus erythematosus

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