Nucleosomes and histones are present in glomerular deposits in human lupus nephritis

in five of 11 patients with DPGN and in two of six patients with MGN. This is the first demonstration of Background. Recently we showed that antinuclear autoantibodies complexed to nucleosomes can bind to nucleosomes in glomerular deposits in SLE nephritis. heparan sulphate (HS) in the glomerular basement Key words: DNA; histones; lupus; nucleosomes; SLE membrane (GBM ) via the histone part of the nucleosome. Histones have been identified in glomerular deposits in human and murine lupus nephritis. In addition, a decreased HS staining in the GBM was Introduction found, most probably due to masking by deposition of antibodies complexed to nucleosomes. In systemic lupus erythematosus (SLE) about 50% of Methods. In this study we first investigated whether patients develop renal disease [1]. Antinuclear antibodhistones or nucleosomes could be identified in glomer- ies and more specifically anti-dsDNA antibodies are ular deposits in human lupus nephritis, and secondly regarded as a hallmark of the disease [2 ]. Since a rise whether the presence of these nuclear components was in titre of anti-dsDNA antibodies often precedes a correlated with absence of HS staining. Kidney biopsies renal exacerbation [3‐5 ] and renal eluates of patients of SLE patients (11 with diffuse proliferative glom- with lupus nephritis are enriched for anti-dsDNA erulonephritis (DPGN) and six with membranous antibodies [6,7], these antibodies are thought to play glomerulonephritis ( MGN )) and of non-SLE glomer- a pathogenic role in the initiation of the glomerular ular diseases were stained for histones, DNA, nucleo- disease. Some years ago we showed that certain antisomes, IgG and HS. dsDNA antibodies are able to bind to heparan sulphate Results. Using a polyclonal anti-H3 1‐21 antiserum, (HS ), an intrinsic constituent of the glomerular basehistones were detected in all patients with DPGN and ment membrane (GBM ). [8 ]. In subsequent experiin two of six patients with SLE-MGN (P<0.01). Using ments we showed that this HS cross-reactivity was a a monoclonal antihistone antibody, histones were property of antibodies complexed to nucleosomal antistained in three patients with DPGN, but in none of gens (i.e. DNA and histones) [9] and that antinucleothe biopsies with MGN. Using nucleosome specific some antibodies complexed to nucleosomal antigens monoclonal antibodies, nucleosomes were detected in were able to bind to HS in the GBM, whereas pure five patients with DPGN, in two patients with MGN, antibodies did not bind [10 ]. but in none of the biopsies with non-SLE glomerulo- In the meantime it was reported that histones are nephritis. HS staining was nearly absent in DPGN, present in immune deposits of both human [11 ] and whereas staining was only moderately reduced in murine [12] lupus nephritis, whereas in murine lupus patients with MGN and controls (P=0.001). an association between histone deposits and albuminConclusion. Using polyclonal and monoclonal antihi- uria was found [12 ]. stone antisera, histones were identified in all patients Recently we found that in the majority of patients with DPGN and their presence was associated with a with lupus nephritis HS staining was absent, whereas decrease of HS staining. Nucleosomes were identified staining for the heparan sulphate proteoglycan