NUCLEOSOMES AND HISTONES ARE PRESENT IN GLOMERULAR DEPOSITS IN HUMAN LUPUS NEPHRITIS

Background. Recently we showed that antinuclear autoantibodies complex ed to nucleosomes can bind to heparan sulphate (HS) in the glomerular basement membrane (GEM) via the histone part of the nucleosome. Histon es have been identified in glomerular deposits in human and murine lup us nephritis. In addition, a decreased HS staining in the GEM was foun d, most probably due to masking by deposition of antibodies complexed to nucleosomes. Methods, In this study we first investigated whether h istones or nucleosomes could be identified in glomerular deposits in h uman lupus nephritis, and secondly whether the presence of these nucle ar components was correlated with absence of HS staining. Kidney biops ies of SLE patients (11 with diffuse proliferative glomerulonephritis (DPGN) and six with membranous glomerulonephritis (MGN)) and of non-SL E glomerular diseases were stained for histones, DNA, nucleosomes, IgG and HS. Results. Using a polyclonal anti-H3 1-21 antiserum, histones were detected in all patients with DPGN and in two of six patients wit h SLE-MGN (P < 0.01). Using a monoclonal antihistone antibody, histone s were stained in three patients with DPGN, but in none of the biopsie s with MGN. Using nucleosome specific monoclonal antibodies, nucleosom es were detected in five patients with DPGN, in two patients with MGN, but in none of the biopsies with non-SLE glomerulonephritis. IIS stai ning was nearly absent in DPGN, whereas staining was only moderately r educed in patients with MGN and controls (P=0.001). Conclusion, Using polyclonal and monoclonal antihistone antisera, histones were identifi ed in all patients with DPGN and their presence was associated with a decrease of HS staining. Nucleosomes were identified in five of 11 pat ients with DPGN and in two of six patients with MGN. This is the first demonstration of nucleosomes in glomerular deposits in SLE nephritis.