Nephrology Dialysis Transplantation, Vol 12, Issue 1 57-66, Copyright © 1997 by Oxford University Press
M van Bruggen, C Kramers, B Walgreen, J Elema, C Kallenberg, J van den Born, R Smeenk, K Assmann, S Muller, M Monestier and J Berden
Background. Recently we showed that antinuclear
autoantibodies Complexed to nucleosomes can bind to heparan sulphate (HS)
in the glomerular basement 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 found, most probably due to masking by deposition of antibodies
complexed to nucleosomes. Methods. In this study we
first investigated whether histones or nucleosomes could be identified in
glomerular deposits in human lupus nephritis, and secondly whether the
presence of these nuclear components was correlated with absence of HS
staining. Kidney biopsies of SLE patients (11 with diffuse proliferative
glomerulonephritis (DPGN) and six with membranous glomerulonephritis (MGN))
and of non-SLE 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 with SLE-MGN (P <0.01(. Using a
monoclonal antihistone antibody, histones were stained in three patients
with DPGN, but in none of the biopsies with MGN. Using nucleosome specific
monoclonal antibodies, nucleosomes were detected in five patients with
DPGN, in two patients with MGN, but in none of the biopsies with non-SLE
glomerulonephritis. HS staining was nearly absent in DPGN, whereas staining
was only moderately reduced in patients with MGN and controls (P=0.001).
Conclusion. Using polyclonal and monoclonal
antihistone antisera, histones were identified in all patients with DPGN
and their presence was associated with a decrease of HS staining.
Nucleosomes were identified in five of 11 patients with DPGN and in two of
six patients with MGN. This is the first demonstration of nucleosomes in
glomerular deposits in SLE nephritis. Keywords: DNA;
histones; lupus; nucleosomes; SLE
ORIGINAL ARTICLES
Nucleosomes and histones are present in glomerular deposits in human lupus nephritis
Division of Nephrology, Department of Pathology, University Hospital Nijmegen, The Netherlands; Pathology and Clinical Immunology, University Hospital Groningen, The Netherlands; Department of Autoimmune Diseases, CLB, Amsterdam, The Netherlands; Institut de Biologie Moleculaire et Cellulaire, CNRS, Strasbourg, France; Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA, USA; Corresponding author at: Division of Nephrology, University Hospital, St Radboud, PO Box 9101, 6500 Nijmegen, The Netherlands
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