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. 1976 Nov 2;144(5):1347–1362. doi: 10.1084/jem.144.5.1347

The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen

PMCID: PMC2190460  PMID: 993727

Abstract

The renal tubular epithelial antigen (Tub-Ag) of rats was solublized by Pronase and purified by gel filtration and acrylamide gel electrophoresis. Purified Tub-Ag was a glycoprotein with S20,W value of 8.4. Utilizing radiolabeled Tug-Ag, a sensitive radioimmunoassay for Tub-Ag and homologous antibody (anti-Tub-Ag) was developed. Tub-Ag activity associated with a protein of the same molecular size was demonstrated in the serum, as well as in Pronase extracts of all the organs tested, including kidney, liver, lung, spleen, intestine, stomach, and heart. The physiochemical properties of the Tub-Ag of rats and its distribution were essentially the same as the Tub-Ag of humans, which had been found in immune deposits in the kidney of some patients with idiopathic membranous glomerulonephritis. Rats were immunized with the purified Tub-Ag emulsified in Freund's complete adjuvant and followed for Tub-Ag and anti-Tub-Ag in the serum, as well as for proteinuria and immunohistological changes in the kidney. Serum Tub-Ag dropped sharply after 20 days, when anti-Tub-Ag appeared in the circulation. Persistent, massive proteinuria appeared still later, more than 30 days after injection, when anti-Tub-Ag disappeared and Tub-Ag reappeared in the serum of some of those rats. In others, anti-Tub-Ag in the serum persisted throughout the observation period of 90 days. The pathology of the kidney of the rats with proteinuria was that of a typical membranous glomerulonephritis; thickening of glomerular capillary walls with granular deposits of gamma-globulin and Tub-Ag was observed. On the basis of these results, Tub-Ag in the serum, probably released from cellular membranes of various organs as a physiological metabolite, is considered to maintain the pathological process in the kidney by providing the antigen continuously to form immune complexes.

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Selected References

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  1. BAXTER J. H., GOODMAN H. C. Nephrotoxic serum nephritis in rats. I. Distribution and specificity of the antigen responsible for the production of nephrotoxic antibodies. J Exp Med. 1956 Oct 1;104(4):467–485. doi: 10.1084/jem.104.4.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braunstein G. D., Lewis E. J., Galvanek E. G., Hamilton A., Bell W. R. The nephrotic syndrome associated with secondary syphilis. An immune deposit disease. Am J Med. 1970 May;48(5):643–648. doi: 10.1016/0002-9343(70)90016-1. [DOI] [PubMed] [Google Scholar]
  3. Combes B., Shorey J., Barrera A., Stastny P., Eigenbrodt E. H., Hull A. R., Carter N. W. Glomerulonephritis with deposition of Australia antigen-antibody complexes in glomerular basement membrane. Lancet. 1971 Jul 31;2(7718):234–237. doi: 10.1016/s0140-6736(71)92572-4. [DOI] [PubMed] [Google Scholar]
  4. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  5. DIXON F. J., FELDMAN J. D., VAZQUEZ J. J. Experimental glomerulonephritis. The pathogenesis of a laboratory model resembling the spectrum of human glomerulonephritis. J Exp Med. 1961 May 1;113:899–920. doi: 10.1084/jem.113.5.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davies D. A., Colombani J., Viza D. C., Hämmerling U. Extraction of HL-A transplantation antigen in high molecular weight soluble form. Clin Exp Immunol. 1971 Jan;8(1):87–90. [PMC free article] [PubMed] [Google Scholar]
  7. Edgington T. S., Glassock R. J., Dixon F. J. Autologous immune complex nephritis induced with renal tubular antigen. I. Identification and isolation of the pathogenetic antigen. J Exp Med. 1968 Mar 1;127(3):555–572. doi: 10.1084/jem.127.3.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edgington T. S., Glassock R. J., Watson J. I., Dixon F. J. Characterization and isolation of specific renal tubular epithelial antigens. J Immunol. 1967 Dec;99(6):1199–1210. [PubMed] [Google Scholar]
  9. Falls W. F., Jr, Ford K. L., Ashworth C. T., Carter N. W. The nephrotic syndrome in secondary syphilis: report of a case with renal biopsy findings. Ann Intern Med. 1965 Dec;63(6):1047–1058. doi: 10.7326/0003-4819-63-6-1047. [DOI] [PubMed] [Google Scholar]
  10. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Glassock R. J., Edgington T. S., Watson J. I., Dixon F. J. Autologous immune complex nephritis induced with renal tubular antigen. II. The pathogenetic mechanism. J Exp Med. 1968 Mar 1;127(3):573–588. doi: 10.1084/jem.127.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HESS E. V., ASHWORTH C. T., ZIFF M. Transfer of an autoimmune nephrosis in the rat by means of lymph node cells. J Exp Med. 1962 Feb 1;115:421–438. doi: 10.1084/jem.115.2.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HEYMANN W., HACKEL D. B., HARWOOD S., WILSON S. G., HUNTER J. L. Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions. Proc Soc Exp Biol Med. 1959 Apr;100(4):660–664. doi: 10.3181/00379727-100-24736. [DOI] [PubMed] [Google Scholar]
  14. HUNTER J. L., HACKEL D. B., HEYMANN W. Nephrotic syndrome in rats produced by sensitization to rat kidney proteins: immunologic studies. J Immunol. 1960 Sep;85:319–327. [PubMed] [Google Scholar]
  15. Koffler D., Agnello V., Thoburn R., Kunkel H. G. Systemic lupus erythematosus: prototype of immune complex nephritis in man. J Exp Med. 1971 Sep 1;134(3 Pt 2):169s–179s. [PubMed] [Google Scholar]
  16. Koffler D., Sandson J., Carr R., Kunkel H. G. Immunologic studies concerning the pulmonary lesions in Goodpasture's syndrome. Am J Pathol. 1969 Feb;54(2):293–305. [PMC free article] [PubMed] [Google Scholar]
  17. Krishnan C., Kaplan M. H. Immunopathologic studies of systemic lupus erythematosus. II. Antinuclear reaction of gamma-globulin eluted from homogenates and isolated glomeruli of kidneys from patients with lupus nephritis. J Clin Invest. 1967 Apr;46(4):569–579. doi: 10.1172/JCI105558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lerner R. A., Glassock R. J., Dixon F. J. The role of anti-glomerular basement membrane antibody in the pathogenesis of human glomerulonephritis. J Exp Med. 1967 Dec 1;126(6):989–1004. doi: 10.1084/jem.126.6.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MELLORS R. C., ORTEGA L. G., HOLMAN H. R. Role of gamma globulins in pathogenesis of renal lesions in systemic lupus erythematosus and chronic membranous glomerulonephritis, with an observation on the lupus erythematosus cell reaction. J Exp Med. 1957 Aug 1;106(2):191–202. doi: 10.1084/jem.106.2.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McCluskey R. T., Vassalli P., Gallo G., Baldwin D. S. An immunofluorescent study of pathogenic mechanisms in glomerular diseases. N Engl J Med. 1966 Mar 31;274(13):695–701. doi: 10.1056/NEJM196603312741301. [DOI] [PubMed] [Google Scholar]
  21. Miyakawa Y., Tanigaki N., Yagi Y., Pressman D. An efficient method for isolation of HL-A antigens from hematopoietic cell lines. J Immunol. 1971 Aug;107(2):394–401. [PubMed] [Google Scholar]
  22. Naruse T., Fukasawa T., Miyakawa Y. Laboratory model of membranous glomerulonephritis in rats induced by pronase-digested homologous renal tubular epithelial antigen. Lab Invest. 1975 Aug;33(2):141–146. [PubMed] [Google Scholar]
  23. SEEGAL B. C., ANDRES G. A., HSU K. C., ZABRISKIE J. B. STUDIES ON THE PATHOGENESIS OF ACUTE AND PROGRESSIVE GLOMERULONEPHRITIS IN MAN BY IMMUNOFLUORESCEIN AND IMMUNOFERRITIN TECHNIQUES. Fed Proc. 1965 Jan-Feb;24:100–108. [PubMed] [Google Scholar]
  24. Strauss J., Pardo V., Koss M. N., Griswold W., McIntosh R. M. Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis. Am J Med. 1975 Mar;58(3):382–387. doi: 10.1016/0002-9343(75)90604-x. [DOI] [PubMed] [Google Scholar]
  25. Sugisaki T., Klassen J., Andres G. A., Milgrom F., McCluskey R. T. Passive transfer of Heymann nephritis with serum. Kidney Int. 1973 Feb;3(2):66–73. doi: 10.1038/ki.1973.13. [DOI] [PubMed] [Google Scholar]
  26. Ward P. A., Kibukamusoke J. W. Evidence for soluble immune complexes in the pathogenesis of the glomerulonephritis of quartan malaria. Lancet. 1969 Feb 8;1(7589):283–285. doi: 10.1016/s0140-6736(69)91038-1. [DOI] [PubMed] [Google Scholar]
  27. Wood B. T., Thompson S. H., Goldstein G. Fluorescent antibody staining. 3. Preparation of fluorescein-isothiocyanate-labeled antibodies. J Immunol. 1965 Aug;95(2):225–229. [PubMed] [Google Scholar]

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