PROLIFERATIVE AUTOIMMUNE GLOMERULONEPHRITIS IN RATS - A MODEL FOR AUTOIMMUNE GLOMERULONEPHRITIS IN HUMANS

Some forms of glomerulonephritis (GN) in humans appear consequent to a utoimmunity. Experimental autoimmune GN (EAG) has been described in sh eep, but attempts to develop EAG in other mammals have resulted only i n antibody and proteinuria but no GN. We have developed a model of EAG in an inbred mammalian species to further study pathogenetic mechanis ms. We immunized Brown Norway (BN) and Wistar-Kyoto (WKY) rats with gl omerular 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 glomeru lar and serum anti GBM antibodies similar to WKY animals. One hundred percent of WKY rats immunized with csGBM/acid developed reproducible s evere GN at two to three weeks with proteinuria and decreased kidney f unction which progressed to glomerulosclerosis and interstitial fibros is. Antigen in acid was a requisite for induction of EAG. EAG rats had positive tests for delayed type hypersensitivity, their T cells under went antigen specific transformation, and T cells and macrophages were present histologically. Passive transfer of EAG serum to naive rats r esulted in fixation to recipient GBM but no proteinuria or GN. This ne w model of EAG in rats appears dependent on genetic factors, may invol ve cellular immunity in pathogenesis, requires exposure of the nephrit ogenic antigen, and is highly similar to rapidly progressive GN in hum ans.