Anti-Histone Reactivity in Systemic Lupus Erythematosus Sera: A Disease Activity Index Linked to the Presence of Dna:Anti-Dna Immune Complexes

Abstract

This study shows that purified murine monoclonal anti-DNA antibodies and human polyclonal anti-DNA antibodies (from systemic lupus erythematosus--SLE--patients), preincubated with DNA, acquire anti-histone reactivity. Conversely, DNAse I treatment of SLE patients' antibodies with anti-histone activity abolishes such activity. It has previously been demonstrated that anti-DNA antibodies bind to the cell membrane and recognize cell-surface polypeptides that have been identified with histones by partial sequencing. In a series of 33 sera from patients with clinically active disease and 29 sera from patients in clinical remission, positivity of an immunoblot analysis detecting antibodies against these polypeptides was associated with clinical activity of SLE (sensitivity, 0.88; specificity, 0.90). Anti-histone reactivity detected by ELISA appeared to be also a good marker of SLE activity (sensitivity, 0.64; specificity, 0.54). As expected, anti-native DNA antibody positivity and lowered complement dosage were also associated with clinical activity (sensitivity, 0.79 and 0.63, respectively; specificity, 0.48 and 0.93, respectively). Since anti-histone reactivity reflects, at least partly, the presence of anti-DNA antibodies complexed to DNA, which could bind to cell-membrane determinants, and is associated with disease clinical activity, it is suggested that this mechanism can contribute to explain the pathogenicity of anti-DNA antibodies.