Binding of anti-DNA antibodies to glomerular heparan sulfate: a new clue for the pathogenesis of SLE nephritis?
Antibodies against heparan sulfate (HS) were detected in sera from patients with active systemic lupus erythematosus (SLE) and in sera from MRL/l mice with a spontaneous SLE-like disease. By inhibition studies it was shown that this reactivity towards HS was due to cross-reactivity of anti-DNA antibodies. Immunoglobulin eluted from human and mouse kidneys with diffuse proliferative SLE glomerulonephritis also bound to HS. This crossreaction of anti-DNA antibodies was further substantiated by the finding that 17 out of 42 anti-DNA monoclonal antibodies (mAb) also bound to HS, 11 out of 17 HS positive mAb bound to heparan sulfate proteoglycan (HSPG) purified from human glomerular basement membranes (GBM) and 7 out of 42 bound directly to isolated human GBM-loops. The binding to HS, HSPG, and GBM could be inhibited in a dose-dependent manner by DNA. In a retrospective analysis of sera from 10 SLE patients, in which 6-16 serum samples per patient were studied, we found in all 5 episodes of onset or exacerbation of a SLE nephritis an anti-HS activity in the serum, prior to onset of the nephritis. In 4 episodes of onset or exacerbation of non-renal manifestations, anti-HS activity was only found in the serum during one episode. Based on these studies we postulate that binding of anti-DNA antibodies to HS within the GBM may be an important immunopathological event in the development of SLE nephritis.
Berden
J H
JH
Department of Nephrology, University of Nijmegen, The Netherlands.
Termaat
R M
RM
Brinkman
K
K
Smeenk
R J
RJ
Swaak
A J
AJ
Faaber
P
P
Assmann
K
K
van de Heuvel
L P
LP
Veerkamp
J H
JH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D004247:DNA / Q000276:immunology*; D006025:Glycosaminoglycans / Q000276:immunology*; D006497:Heparan Sulfate / Q000276:immunology*; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004247:DNA; D006025:Glycosaminoglycans; D006497:Heparan Sulfate