R Suenaga1, N I Abdou. 1. Immunology Research Laboratory, St. Luke's Hospital, Kansas City, Missouri 64111, USA.
Abstract
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.
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.
Authors: Bruce K Tan; Quan-Zhen Li; Lydia Suh; Atsushi Kato; David B Conley; Rakesh K Chandra; Jinchun Zhou; James Norton; Roderick Carter; Monique Hinchcliff; Kathleen Harris; Anju Peters; Leslie C Grammer; Robert C Kern; Chandra Mohan; Robert P Schleimer Journal: J Allergy Clin Immunol Date: 2011-10-13 Impact factor: 10.793