This research is concerned with a study of the pathogenesis of renal disease in children especially disorder leading to significant glomerular injury and the ultimate development of renal failure - glomerulonephritis, nephrotic syndrome, familial renal disease and other diseases. A major objective is a comprehensive, morphologic and immunohistochemical investigation of the glomerular capillary which our prior studies have shown to be more heterogeneous than previously recognized. These studies will include immunologic, biochemical and histochemical analysis of the glomerular polyanion, proteoglycans, as well as other antigens, which reside in an inner antigenic array along or within the lamina densa. Normal and diseased kidneys will be studied using immunohistochemical techniques with heterologous and monoclonal antibodies. a second major objective is concerned with an evaluation of immunopathologic mechanisms that play a role in renal disease. In particular, these studies will extend our recent observations in IgA nephropathy that only monomeric IgA1 (and not IgA2) is present in the mesangium and that in this disease there is a higher than normal association with a B cell antigen. The relative IgA subclass serum levels and response of lymphocytes from these patients, will be studied and related to a characterization of the B cell antigen in order to define whether the latter reflects an IgA immune response determinant. In addition, studies of the Fc receptor of circulating phagocytes in renal disease using an in vitro assay involving pre-formed immune compleses will permit quantitation of the Fc receptor of monocytes in various disease states.
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