Oral administration of glomerular basement membrane prevents the development of experimental autoimmune glomerulonephritis in the WKY rat.
Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by a single injection of collagenase-solubilized rat glomerular basement membrane (GBM) in adjuvant. EAG is characterized by circulating and deposited anti-GBM antibodies, accompanied by focal necrotizing glomerulonephritis with crescent formation. The inhibitory effect of orally administered antigens has been reported in various animal models of autoimmunity but not in EAG in the rat. The effects of feeding rat GBM by gavage, at total doses of 0.5, 2.5, or 5 mg, before immunization were examined. A dose-dependent effect was observed on the development of EAG. A dose of 0.5 mg of GBM had no effect on disease, 2.5 mg resulted in a moderate reduction in the severity of nephritis but no change in anti-GBM antibody production, and 5 mg resulted in a marked reduction in circulating and deposited anti-GBM antibodies, albuminuria, deposits of fibrin in the glomeruli, severity of glomerular abnormalities, and numbers of infiltrating T cells and macrophages. Animals that were fed 5 mg of GBM showed a significant reduction in IgG2a but not IgG1, anti-GBM antibody levels, suggesting downregulation of Th1 responses. There was also a dose-dependent reduction in the proliferative responses of splenic T cells from treated animals to GBM antigen in vitro. These results clearly demonstrate that mucosal tolerance can be induced by oral administration of GBM antigen and that this approach is effective in preventing EAG.
Reynolds
John
J
Renal Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Pusey
Charles D
CD
Renal Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
D000284:Administration, Oral; D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000008:administration & dosage*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D001485:Basement Membrane / Q000276:immunology; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D003404:Creatinine