Binding characteristics of SLE anti-DNA autoantibodies to Catecholestrogen-modified DNA.
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.
Khan
W A
WA
Department of Biochemistry, Faculty of Medicine, J. N. Medical College, AMU, Aligarh, India. wahidalikhan@rediffmail.com
D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D004247:DNA / Q000737:chemistry / Q000276:immunology*; D024202:Electrophoretic Mobility Shift Assay; D004958:Estradiol / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology; D002393:Estrogens, Catechol / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002393:Estrogens, Catechol; D004958:Estradiol; D004247:DNA; C014036:4-hydroxyestradiol