The main objective of the project is to investigate the pathogenesis of membranous glomerulonephritis, which is a fairly common form of chronic renal disease in man. Although the disease is assumed to result from deposition of immune complexes in glomeruli, the identity of tha antigen(s) and the specificities of the antibodies in the deposits are unknown. The hypothesis to be tested is that the glomerular deposits result from the interaction of autoantibodiees with antigens on the surface of glomerular epithelial cells. This hypothesis is based on findings in Heymann nephritis, an experimental model in rats that closely resembles the human disease. Autoantibodies reactive with glomerular epithelial cells will be sought in patients with membranous nephritis, by the use of approaches developed in studies on Heymann nephritis, in particular by the use of cultured glomerular epithelial cells as substrates. In addition, monoclonal antibodies will be prepared by immunization of mice with antigen preparations obtained from normal renal tissue or from specimens of membranous nephritis, with the aim of obtaining antibodies that identify nephritogenic antigens. Other studies will be concerned with heymann nephritis. The nature and possible interaction of two identified nephritogenic antigens (gp 330 and a 95 kd antigen) will be investigated, in particular with respect to the mechanism of formation of glomerular deposits. In addition, the degree of idiotypic heterogeneity of the autoantibodies will be studied, and experiments will be performed to determine if antiidiotypic antibodies can modify Heymann nephritis.
| Gutmann, E J; Niles, J L; McCluskey, R T et al. (1991) Loss of antigens associated with the apical endocytotic pathway in proximal tubules from rats with heymann nephritis. Am J Pathol 138:1243-55 |
| Niles, J L; McCluskey, R T; Ahmad, M F et al. (1989) Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase. Blood 74:1888-93 |
| Raychowdhury, R; Niles, J L; McCluskey, R T et al. (1989) Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor. Science 244:1163-5 |
| Gutmann, E J; Niles, J L; McCluskey, R T et al. (1989) Colchicine-induced redistribution of an apical membrane glycoprotein (gp330) in proximal tubules. Am J Physiol 257:C397-407 |
| Kurnick, J T; McCluskey, R T; Bhan, A K et al. (1988) Escherichia coli-specific T lymphocytes in experimental pyelonephritis. J Immunol 141:3220-6 |
