Production of Heymann nephritis by a chemically modified renal antigen

Int J Exp Pathol. 2004 Oct;85(5):277-85. doi: 10.1111/j.0959-9673.2004.00389.x.

Abstract

An autoimmune kidney disease morphologically and functionally similar to Heymann nephritis (HN) was induced in mature male Sprague Dawley rats by repeated weekly IP injections of a chemically modified azo sonicated ultracentrifuged (u/c) rat kidney fraction 3 (rKF3) antigen in an aqueous medium. The experiment was terminated 15 weeks after the first injection of the chemically altered antigen. Serum samples collected and analysed by an indirect fluorescent antibody test on normal rat kidney sections during the course of the experiment showed a gradual rise in circulating pathogenic autoantibodies directed against the proximal tubular brush border regions. Proteinuria was present and significantly increased in the urine of two of eight rats. The arising immune-complex glomerulonephritis (ICGN) revealed typical HN kidney disease lesions in 70% of the rats in histological, direct fluorescent antibody and electron-microscopical examinations. Control rats injected similarly with the an unmodified version of the same antigen did not develop the HN-characteristic morphological and functional changes. To our knowledge, this is the first time that the autoimmune kidney disease designated as an active HN has been produced by the administration of a chemically altered renal antigen in an aqueous solution and not by the usual presentation of the nephritogenic renal antigen in an adjuvant.

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Fluorescent Antibody Technique, Direct / methods
  • Fluorescent Antibody Technique, Indirect / methods
  • Glomerulonephritis / complications
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Heymann Nephritis Antigenic Complex / immunology*
  • Immune Complex Diseases / complications
  • Immune Complex Diseases / immunology
  • Immune Complex Diseases / pathology
  • Immunoglobulin G / analysis
  • Immunoglobulin M / analysis
  • Kidney / immunology
  • Kidney / pathology
  • Male
  • Microscopy, Electron
  • Microvilli / immunology
  • Proteinuria / complications
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Autoantibodies
  • Heymann Nephritis Antigenic Complex
  • Immunoglobulin G
  • Immunoglobulin M