Most forms of glomerulonephritis are initiated by immune complex-mediated injury. Immune complex deposition in the glomerulus has been shown to result from both in situ formation and trapping of circulating immune complexes. It is the purpose of this proposal to investigate the role of an additional mechanism of glomerular immune complex formation. It is suggested that in the Heymann rat model of membranous nephropathy, a circulating antigen binds to a glomerular antigen via internal images. Immunization with the circulating antigen results in production of primary antibody and anti-idiotypic antibody. A subset of the anti-idiotypic antibodies will bear the appropriate internal image, will mimic the immunizing antigen, and thus will bind to the glomerular antigen. To investigate this hypothesis, the 2 antigens and primary and anti-idiotypic antibodies will be isolated and their binding via internal images will be determined. Demonstration that a circulating antigen binds to a glomerular antigen with subsequent antibody deposition would explain the subepithelial localization of immune deposits in membranous nephropathy. In addition, the production of anti-idiotypic antibodies that mimic antigen has been postulated to contribute to the development of autoimmunity. Confirmation of the internal image relationships in the putative antigens of Heymann nephritis offers the opportunity to evaluate this postulate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035142-04
Application #
3233393
Study Section
Pathology A Study Section (PTHA)
Project Start
1984-07-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Abrass, C K; Berfield, A K; Stehman-Breen, C et al. (1999) Unique changes in interstitial extracellular matrix composition are associated with rejection and cyclosporine toxicity in human renal allograft biopsies. Am J Kidney Dis 33:11-20
Hansen, K M; Berfield, A K; Spicer, D et al. (1998) Rat mesangial cells express two unique isoforms of laminin which modulate mesangial cell phenotype. Matrix Biol 17:117-30
Berfield, A K; Raugi, G J; Abrass, C K (1996) Insulin induces rapid and specific rearrangement of the cytoskeleton of rat mesangial cells in vitro. J Histochem Cytochem 44:91-101
Abrass, C K; Berfield, A K (1995) Phenotypic modulation of rat glomerular visceral epithelial cells by culture substratum. J Am Soc Nephrol 5:1591-9
Abrass, C K; Adcox, M J; Raugi, G J (1995) Aging-associated changes in renal extracellular matrix. Am J Pathol 146:742-52
Abrass, C K; Spicer, D; Raugi, G J (1994) Insulin induces a change in extracellular matrix glycoproteins synthesized by rat mesangial cells in culture. Kidney Int 46:613-20
Gauthier, V J; Abrass, C K (1992) Circulating immune complexes in renal injury. Semin Nephrol 12:379-94
Hori, M T; Abrass, C K (1990) Isolation and characterization of circulating immune complexes from rats with experimental membranous nephropathy. J Immunol 144:3849-55
Abrass, C K; Cohen, A H (1988) Characterization of renal injury initiated by immunization of rats with heparan sulfate. Am J Pathol 130:103-11