The studies supported by this grant are designed to increase our understanding of the immunologic processes responsible for glomerulonephritis and tubulointerstitial nephritis, occurring as a primary disease or developing after renal transplation. These immune mechanism are a leading cause of renal failure. The studies utilize serum and renal tissue submitted by contributing nephrology and transplant-related nephrology programs throghout the United State and provide a clinical-immunopathological data base to determine incidence, course, management, initiating factors, etc., of the various nephritogenic processes evaluated. The planned studies interdigitate with our ongoing animal-based studies dealing with the nature of nephritogenic immune processes include classical anti-glomerular basement membrane (GBM) and anti-tubular basement antibodies, and potentially nephritogenic reactions of antibodies reactive with nonclassical GBM glomerular capillary wall antigens, as identified in animal models under study. Characterization of reactive antigens and antibodies employ standard radioimmunoassay and physical-chemical techniques, as well as enlisting new technologies with monoclonal and anti-idiotypic antibodies. Familial and genetic features, as they may relate to differences in antigens and antibodies, are under study. Experiments also will be initiated to interrupt the specific immune responses. Efforst continue to identify specific antigen-antibody systems responsible for immune complex form of glomerular injury, as well as to utilize assays for circulating immune complexes to sequentially study patients. Mediators of immunologic renal injury will be evaluated through direct measurement of intrarenal effects (physiologic and morpho-immunopathologic) of infusion of activated mediators of immune renal injury in animals and by identifying cellular elements of the immune system and their interactions with monocytes and macrophages in man; the latter cell types were recently demonstrated to be prominent mediators in certain stages of experimental immune renal injury. Studies also will be pursued to increase our understanding of the factors which may influence progression of immunologically iniacted injury, an area of great importance but one about which little is known.
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