Genetic control of susceptibility to autologous immune complex glomerulonephritis in inbred rat strains

Abstract

Twelve inbred rat strains were tested for their susceptibility to autologous immune complex glomerulonephritis (AIC) after a single injection of a primary tubular epithelial fraction emulsified in Freund's complete adjuvant. Six strains (Lewis, AS, BDV, L.BDV, AS2, L.AS2) showed high responsiveness in terms of proteinuria and immunohistological changes, which could be observed after 3 months. Strains BN, AVN and DA were completely resistant, even after 6 months of observation. An additional adjuvant (pertussis vaccine) did not break non-responsiveness in one of these strains (BN). Strains which share the Lewis strain genetic background (L.BN, L.AVN and L.WP) seemed to be at least weakly susceptible to AIC. A close association between susceptibility and the major histocompatibility haplotypes is demonstrated in segregation studies involving Lewis, L.BN and BN rats. A threshold model of AIC susceptibility, based on the action of major histocompatibility-linked genes and background genes, is suggested.