Recognition of oxidized DNA bases by sera of patients with inflammatory diseases

Chronic inflammatory conditions result from or contribute to many diseases. Prominent among them is systemic lupus erythematosus (SLE). Sera of SLE patients contain an array of various auto-antibodies (Ab), including antinuclear Ab of unknown etiologies. The most puzzling is formation of Ab directed against autologous DNA. Our hypothesis was that increased oxidant production causes oxidation of DNA bases, which provide antigenic determinants that elicit antioxidized DNA Ab. To test this hypothesis, we used oxidized DNA nucleoside (5-hydroxymethyl-2'-deoxyuridine [HMdU]) conjugated to bovine serum albumin (HMdU-BSA) as the antigen. The results of the enzyme-linked immunosorbent assay showed that these Abs are sensitively detectable in SLE sera and sera of various other inflammatory autoimmune diseases. The titers of anti-HMdU Ab were significantly higher (p < .01) than those present in the control sera. Anti-HMdU Ab were predominantly of the IgM isotype, with low levels of IgG and no IgA. Anti-HMdU Ab bound to the HMdU-BSA-coated wells in a concentration- and time-dependent manner. That binding was inhibited by HMdU-BSA and to a lesser extent by thymidine-BSA, a normal nucleoside conjugate. The specific binding appears to be inversely related to the age of the patients, but no significant differences were observed between the sexes of the same age.