Free radical mediated peroxidative damage in systemic lupus erythematosus.
Free radicals and damage caused by these molecular species are implicated in the pathogenesis of a variety of diseases, including autoimmune. Here we have examined oxidative damage, SOD activity and autoantibodies against SOD in systemic lupus erythematosus (SLE), a multifactorial disease with autoantibody production as an universal feature. We found significantly increased amounts of conjugated dienes in the SLE patients compared to normals (mean value of 0.917 vs 0.627, p = 0.0001) and MDA formation (6.96 vs 4.17 nmoles/microl, p = 0.0006) as well as decreased SOD activity. In addition, we found autoantibodies binding SOD by both ELISA and immunoblot. The presence of anti-SOD antibodies was associated with increased free radical damage in SLE patients. Heat inactivated anti-SOD autoantibodies were able to inhibit the activity of the enzyme. We propose that the inhibition of SOD by autoantibodies is, in part, responsible for the increased free radical damage seen in the disease.
Kurien
Biji T
BT
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Scofield
R Hal
RH
D001323:Autoantibodies / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005609:Free Radicals / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000276:immunology; D008054:Lipid Peroxides / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D013482:Superoxide Dismutase / Q000276:immunology / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D001323:Autoantibodies; D005609:Free Radicals; D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D013482:Superoxide Dismutase