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 Goodpa sture's disease, can be induced in Wistar Kyoto (WKY) rats by a single inje ction of collagenase-solubilized rat glomerular basement membrane (GBM) in adjuvant. EAG is characterized by circulating and deposited anti-GBM antibo dies, accompanied by focal necrotizing glomerulonephritis with crescent for mation. The inhibitory effect of orally administered antigens has been repo rted in various animal models of autoimmunity but not in EAG in the rat. Th e 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 o n 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 n o change in anti-GBM antibody production, and 5 mg resulted in a marked red uction in circulating and deposited anti-GBM antibodies, albuminuria, depos its of fibrin in the glomeruli, severity of glomerular abnormalities, and n umbers 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 antib ody levels, suggesting downregulation of Th1 responses. There was also a do se-dependent reduction in the proliferative responses of splenic T cells fr om treated animals to GBM antigen in vitro. These results clearly demonstra te that mucosal tolerance can be induced by oral administration of GBM anti gen and that this approach is effective in preventing EAG.