Abstract
Non-enzymatic lipid peroxidation of cellular membranes occurs during periods of sustained oxidative stress. 4-Hydroxynonenal (HNE), the most reactive lipid peroxidation product, is capable of modifying and/or cross-linking proteins leading to impaired physiological functions. The formation of protein adducts produce structural modifications which generate neo-antigens and induce auto-antibodies. Enhanced oxidative stress and accumulation of HNE-modified proteins are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. This study has probed the role of lipid peroxidation derived aldehydes in SLE. We report the structural perturbations in human serum albumin (HSA) upon modification with HNE and the consequential enhanced immunogenicity. The induced antibodies were found to be highly specific for the immunogen and exhibited cross-reactivity with HNE-modified epitopes on proteins, amino acids and nucleic acid. The experimentally induced anti-HNE-HSA antibodies appreciably recognized HNE modified epitopes on the HSA obtained from SLE patients. These antibodies, therefore, form a good immunochemical probe to detect such damages in lupus patients. Possible role of anti-HNE-HSA antibodies as a marker for detection/progression of SLE has been discussed.