ANTI-(DNA-HISTONE) ANTIBODIES IN ACTIVE LUPUS NEPHRITIS

Objective. To detect and characterize anti-(DNA-histone) antibodies in patients with active lupus nephritis. Methods. Calf thymus double str anded DNA was reassociated with histone in vitro. Polynucleosomes were prepared from chicken erythrocyte nuclei, calf thymus nucleohistone, and human peripheral blood mononuclear cells. Anti-DNA activity was de pleted from purified IgG using DNA-cellulose. Binding of the adsorbed IgG to various (DNA-histone) related antigens was measured by ELISA. A ntigen specificity was assessed by inhibition assays and adsorption st udies using histone and nucleosome conjugated sepharose beads. Results . Anti-(DNA-histone) antibodies were detected in 3 of 5 patients with active lupus nephritis. They specifically recognized determinants cons isting of both DNA and histone, but not DNA or histone alone. Anti-(DN A-histone) antibodies largely overlapped with antinucleosome antibodie s and appeared to react with nucleosomes released by apoptotic human m ononuclear cells. Conclusion. Anti-(DNA-histone) antibodies are presen t in active lupus nephritis and largely represent antinucleosome antib odies. They may contribute to the pathogenesis of nephritis by forming immune complexes with apoptosis related nucleosomes.