Oxidized low-density lipoprotein and beta2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness: implications in autoimmune-mediated atherosclerosis.
Oxidative stress and LDL modification (oxLDL) are early pro-atherogenic events. OxLDL binds beta2GPI producing immunogenic oxLDL/beta2GPI complexes. Antibodies to these complexes have been associated with arterial thrombosis in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Circulating oxLDL/beta2GPI 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 (OD450nm) for oxLDL/beta2GPI complexes in SLE was 0.244 +/- 0.07, higher than controls (0.174 +/- 0.09, P < 0.001). Median OD for IgG anti-oxLDL/beta2GPI 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/beta2GPI 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/beta2GPI complexes and IgG (not IgM) anti-oxLDL/beta2GPI antibodies contribute to the development of autoimmune-mediated atherosclerosis.
Lopez
L R
LR
Corgenix, Inc., Westminster, Colorado, USA. llopez@corgenix.com
Salazar-Paramo
M
M
Palafox-Sanchez
C
C
Hurley
B L
BL
Matsuura
E
E
Garcia-De La Torre
I
I
D000293:Adolescent; D000328:Adult; D001053:Apolipoproteins / Q000097:blood*; D050197:Atherosclerosis / Q000209:etiology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012307:Risk Factors; D017539:Tunica Intima / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology; D053482:beta 2-Glycoprotein I
D001053:Apolipoproteins; D001323:Autoantibodies; D015415:Biomarkers; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein