4-hydroxyestradiol and Lupus-Erythematosus--Systemic

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which anti-double-stranded DNA antibody is a classic autoantibody that characterizes SLE. A role for oestrogens in the pathogenesis of SLE has been suspected for many years but the exact patho-aetiology remains elusive. In this study, the binding of SLE autoantibodies with native and 4-OHE(2)-NO-modified plasmid DNA were assessed. Binding specificity of antibodies was analysed by direct binding and inhibition enzyme-linked immunosorbent assay, quantitative precipitin titration and gel retardation assay. Anti-DNA IgG from SLE sera, purified on Protein A-Agarose matrix, exhibited increased recognition of 4-OHE(2)-NO-DNA than native DNA (P < 0.001). Gel retardation assay further substantiated the enhanced recognition of modified DNA by anti-DNA autoantibodies. The affinity of anti-DNA antibodies for modified polymer was found to be high as calculated by using Langmuir plot. DNA modified by 4-OHE(2)-NO presents unique neo-epitopes that might be one of the factor in antigen-driven induction of SLE autoantibodies.

Topics: Antibodies, Antinuclear; Antibody Specificity; Autoantibodies; DNA; Electrophoretic Mobility Shift Assay; Estradiol; Estrogens, Catechol; Humans; Lupus Erythematosus, Systemic