Binding of circulating SLE autoantibodies to oxygen free radical damaged chromatin

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various immunologic disorders, including production of autoantibodies, formation of immune complexes, decreased serum complement levels, and lymphocytopenia. One of the hallmarks of this disease is the loss of tolerance to nuclear antigens. The dominant presence of antibodies against the exposed conformational epitopes on chromatin strongly suggests that the pathogenic immune response in lupus is driven by chromatin. In the present study, the binding of SLE autoantibodies with native chromatin and oxygen free radical damaged chromatin was studied. As assessed by direct binding and inhibition ELISA, circulating SLE autoantibodies exhibited a high degree of specificity towards the reactive oxygen species (ROS)-modified chromatin in comparison to native chromatin and this binding specificity was reiterated visually by gel retardation assay. The data suggested possible role of modified chromatin in the induction of SLE autoantibodies and higher recognition of oxidatively damaged chromatin by antibodies in sera of SLE patients. It is indicated that free radical modified chromatin or nucleosomes might be the antigen for the production of circulating autoantibodies in SLE.