Proliferative autoimmune glomerulonephritis in rats: a model for autoimmune glomerulonephritis in humans.
Some forms of glomerulonephritis (GN) in humans appear consequent to autoimmunity. Experimental autoimmune GN (EAG) has been described in sheep, but attempts to develop EAG in other mammals have resulted only in antibody and proteinuria but no GN. We have developed a model of EAG in an inbred mammalian species to further study pathogenetic mechanisms. We immunized Brown Norway (BN) and Wistar-Kyoto (WKY) rats with glomerular basement membrane (GBM) or collagenase solubilized GBM (csGBM). Circulating and bound anti-GBM antibody developed in all rats. Only interstitial nephritis occurred in BN rats despite amounts of glomerular and serum anti GBM antibodies similar to WKY animals. One hundred percent of WKY rats immunized with csGBM/acid developed reproducible severe GN at two to three weeks with proteinuria and decreased kidney function which progressed to glomerulosclerosis and interstitial fibrosis. Antigen in acid was a requisite for induction of EAG. EAG rats had positive tests for delayed type hypersensitivity, their T cells underwent antigen specific transformation, and T cells and macrophages were present histologically. Passive transfer of EAG serum to naive rats resulted in fixation to recipient GBM but no proteinuria or GN. This new model of EAG in rats appears dependent on genetic factors, may involve cellular immunity in pathogenesis, requires exposure of the nephritogenic antigen, and is highly similar to rapidly progressive GN in humans.
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville.
W K
WK
Bolton
W J
WJ
May
B C
BC
Sturgill
D000818:Animals; D000917:Antibody Formation; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001485:Basement Membrane / Q000276:immunology; D004195:Disease Models, Animal; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D007116:Immunization, Passive; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology; D008297:Male; D010641:Phenotype; D051381:Rats; D011921:Rats, Inbred WKY