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 stranded 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 depleted from purified IgG using DNA-cellulose. Binding of the adsorbed IgG to various (DNA-histone) related antigens was measured by ELISA. Antigen specificity was assessed by inhibition assays and adsorption studies 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 consisting of both DNA and histone, but not DNA or histone alone. Anti-(DNA-histone) antibodies largely overlapped with antinucleosome antibodies and appeared to react with nucleosomes released by apoptotic human mononuclear cells.

Conclusion: Anti-(DNA-histone) antibodies are present in active lupus nephritis and largely represent antinucleosome antibodies. They may contribute to the pathogenesis of nephritis by forming immune complexes with apoptosis related nucleosomes.