Character of anti-DNA antibodies in systemic lupus erythematosus.

Anti-DNA antibodies in twenty-one systemic lupus erythematosus (SLE) sera were analysed by precipitation in gel, complement fixation, and the Farr globulin precipitation technique. Fifteen sera precipitated in agarose with both native and denatured DNA (Group 1) and six precipitated solely with denatured DNA (Group 2). Prior incubation of the sera with RNA or DNA digest abolished the precipitin reactions of all Group 2 sera, but had no appreciable effect on the precipitin patterns of the Group 1 sera. Molecular class of anti-DNA antibodies did not correlate with precipitation pattern. The ability of sucrose density gradient fractions of serum to fix complement with denatured DNA at 4°C did not correspond with the presence of precipitating antibodies against denatured DNA. The Farr globulin binding assay probably allowed detection of all anti-DNA antibodies, and each of the sera bound most of the [14C]DNA. No binding was observed when 14C-labelled nucleotides were substituted for the [14C]DNA. Both native and denatured unlabelled DNA were able to significantly inhibit binding by all sera tested (Groups 1 and 2), while RNA and DNA digest gave minimal inhibition. Three types of antigenic sites on the DNA molecule are postulated. It is suggested that all anti-DNA sera, regardless of their behaviour in precipitin or complement fixation tests, contain antibodies reactive with all three determinants on the DNA molecule.