Glomerulonephritis induced by recombinant collagen IV alpha 3 chain noncollagen domain 1 is not associated with glomerular basement membrane antibody: a potential T cell-mediated mechanism.
Glomerulonephritis is believed to result commonly from Ab-mediated glomerular injury. However, Ab-associated mechanisms alone cannot explain many cases of human glomerulonephritis. We developed a rat model of human anti-glomerular basement membrane (GBM) disease to investigate T cell and Ab response, and their associations with the disease. A single immunization of highly denatured recombinant mouse collagen IV alpha3 chain noncollagen domain 1 (rCol4alpha3NC1) induced severe glomerulonephritis in 100% of Wistar Kyoto rats, 33% of which died of this disease around day 35 postimmunization. The renal pathology demonstrated widespread glomerular damage and a mononuclear cell infiltration within the interstitial tissue. T cells from immunized rats responded not only to rCol4alpha3NC1, but also to isolated rat GBM. Sera Abs to rCol4alpha3NC1 were detectable in 100% of the rats, but only 20% of the rats had low levels of Ab to isolated rat GBM by Western blot, and none by immunofluorescence. Furthermore, IgG/M binding to or C3 deposition on endogenous GBM in immunized rats were not detected in most of the experimental rats, and showed no statistical correlation with disease severity. Additionally, no electronic dense deposition in the glomeruli was detected in all rats. Those data revealed a disassociation between the disease and anti-GBM Ab. T cell-mediated mechanisms, which are currently under our investigation, may be responsible for the glomerular disease.
Wu
J
J
Department of Basic Sciences, Dental Branch, University of Texas Houston Health Science Center, Houston, TX 77030, USA.
Hicks
J
J
Ou
C
C
Singleton
D
D
Borillo
J
J
Lou
Y H
YH
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000737:chemistry; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology; D024141:Collagen Type IV / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007678:Kidney Glomerulus / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D011994:Recombinant Proteins