Peroxynitrite-modified DNA: a better antigen for systemic lupus erythematosus anti-DNA autoantibodies

Abstract

Native human DNA was modified by ONOO- (peroxynitrite), generated by the synergistic action of sodium nitroprusside [Na2Fe(CN)5NO], an NO donor, and pyrogallol, a superoxide donor. The modifications were analysed by UV absorption characteristics, fluorescence emission transitions, nuclease S1 digestibility and melting-temperature studies. Modified DNA was found to be highly immunogenic, inducing high-titre immunogen-specific antibodies in experimental animals. A maximum of 85% inhibition of the antibody binding was observed in competition ELISA with immunogen as inhibitor. SLE (systemic lupus erythematosus) anti-DNA autoantibodies recognized modified DNA as a better antigen than the native analogue. Modification of native DNA by ONOO-, forming neo-epitopes on the molecule, may be one of the factors for the induction of the autoimmune response seen in SLE.