Significance of Oxidative and Nitrosative Stress in Systemic Lupus Erythematosus

Abstract

Autoimmune diseases (ADs) such as systemic lupus erythematosus (SLE) and rheumatoid arthritis are chronic and life‐threatening disorders. Despite high prevalence of these diseases, molecular mechanisms underlying systemic autoimmune response remain largely unknown. Previous studies in our laboratory using an autoimmune‐prone MRL+/+ mice suggested an association between oxidative/nitrosative stress and autoimmunity. However, relevance of oxidative/nitrosative stress in disease prognosis and pathogenesis in humans is not understood. To investigate the status of oxidative/nitrosative stress in ADs, sera from 20 SLE patients and 20 age‐ and gender‐matched healthy subjects (controls) were evaluated for oxidative/nitrosative stress markers. Serum analysis showed not only higher levels of both anti‐malondialdehyde (MDA) and anti‐4‐hydroxynonenal (HNE)‐protein adduct antibodies, reflecting increased formation of lipid peroxidation‐derived aldehydes (MDA and HNE) and their conjugation to endogenous proteins. Serum Cu/Zn superoxide dismutase (an antioxidant enzyme) levels were significantly reduced in patients with SLE compared to controls, suggesting a compromised antioxidant balance. Furthermore, sera from SLE patients had significantly higher levels of iNOS and nitrotyrosine, suggesting nitrosative stress in these patients. These findings further support an association between oxidative/nitrosative stress and SLE, and suggest that oxidative/nitrosative stress markers may be useful in evaluating the prognosis of SLE as well as in elucidating the mechanisms of disease pathogenesis.