Genetic control of autoimmune tubulointerstitial nephritis in rats

Immunization of inbred rat strains with sheep TBM leads to anti-TBM antibody production in all strains tested, indicating their high responsiveness to this antigen. In contrast only certain strains express the relevant TBM antigen as demonstrable by binding of anti-TBM antibody in a linear fashion to the TBM, a process which leads to an autoimmune tubulointerstitial nephritis with increased BUN values. The expression of this TBM antigen is independent of the MHS and is controlled by one dominant gene as is shown by the strain distribution pattern and segregation analysis. Homologous immunization with rat TBM leads to an autoimmune response and to the disease only when preparations of TBM antigen-positive rat strains are applied. The inducibility of autoimmune tubulointerstitial nephritis in the rat strains tested, therefore, is determined by a gene controlling the presence of the target antigen rather than the immune response to it.