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. 1983 Oct;113(1):19–26.

Experimental cholestasis promotes the deposition of glomerular IgA immune complexes.

S N Emancipator, G R Gallo, R Razaboni, M E Lamm
PMCID: PMC1916307  PMID: 6194689

Abstract

Previous experimental and clinical studies support a role for the hepatobiliary system in the clearance of oligomeric IgA from serum, and alterations of this system have been associated with the deposition of IgA in the renal mesangium. The present studies in mice address the question of whether the mesangial deposition of IgA following cholestasis includes immune complexes. While bile duct ligation resulted in mesangial IgA deposition within several days in approximately 75% of animals, whether deliberately orally immunized, nonimmunized, or given injected immune complexes, mice that underwent sham operations had IgA deposits only if orally immunized. Moreover, mice that had been orally immunized or given injected immune complexes and whose bile ducts had been ligated contained deposits of specific IgA antibody and antigen. In the ligated mice some of the IgA was secretory IgA, as demonstrated by the presence of secretory component. Thus, bile duct ligation promotes the deposition of circulating IgA immune complexes, presumably by decreasing their clearance from serum, and gives rise to secretory IgA in the glomerular mesangium. The secretory immune system probably plays a role in the pathogenesis of idiopathic and cirrhosis-related human IgA nephropathy.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berger J., Yaneva H., Nabarra B. Glomerular changes in patients with cirrhosis of the liver. Adv Nephrol Necker Hosp. 1977;7:3–14. [PubMed] [Google Scholar]
  2. Brown T. A., Russell M. W., Mestecky J. Hepatobiliary transport of IgA immune complexes: molecular and cellular aspects. J Immunol. 1982 May;128(5):2183–2186. [PubMed] [Google Scholar]
  3. Callard P., Feldmann G., Prandi D., Belair M. F., Mandet C., Weiss Y., Druet P., Benhamou J. P., Bariety J. Immune complex type glomerulonephritis in cirrhosis of the liver. Am J Pathol. 1975 Aug;80(2):329–340. [PMC free article] [PubMed] [Google Scholar]
  4. Cantarero L. A., Butler J. E., Osborne J. W. The adsorptive characteristics of proteins for polystyrene and their significance in solid-phase imunoassays. Anal Biochem. 1980 Jul 1;105(2):375–382. doi: 10.1016/0003-2697(80)90473-x. [DOI] [PubMed] [Google Scholar]
  5. EISEN H. N. PREPARATION OF PURIFIED ANTI-2,4-DINITROPHENYL ANTIBODIES. Methods Med Res. 1964;10:94–102. [PubMed] [Google Scholar]
  6. Emancipator S. N., Gallo G. R., Lamm M. E. Experimental IgA nephropathy induced by oral immunization. J Exp Med. 1983 Feb 1;157(2):572–582. doi: 10.1084/jem.157.2.572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Engvall E. Enzyme immunoassay ELISA and EMIT. Methods Enzymol. 1980;70(A):419–439. doi: 10.1016/s0076-6879(80)70067-8. [DOI] [PubMed] [Google Scholar]
  8. Gallo G. R., Caulin-Glaser T., Lamm M. E. Charge of circulating immune complexes as a factor in glomerular basement membrane localization in mice. J Clin Invest. 1981 May;67(5):1305–1313. doi: 10.1172/JCI110159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gormly A. A., Smith P. S., Seymour A. E., Clarkson A. R., Woodroffe A. J. IgA glomerular deposits in experimental cirrhosis. Am J Pathol. 1981 Jul;104(1):50–54. [PMC free article] [PubMed] [Google Scholar]
  10. Heidelberger M., Kendall F. E., Soo Hoo C. M. QUANTITATIVE STUDIES ON THE PRECIPITIN REACTION : ANTIBODY PRODUCTION IN RABBITS INJECTED WITH AN AZO PROTEIN. J Exp Med. 1933 Jul 31;58(2):137–152. doi: 10.1084/jem.58.2.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hyman L. R., Wagnild J. P., Beirne G. J., Burkholder P. M. Immunoglobulin-A distribution in glomerular disease. Analysis of immunofluorescence localization and pathogenetic significance. Kidney Int. 1973 Jun;3(6):397–408. doi: 10.1038/ki.1973.62. [DOI] [PubMed] [Google Scholar]
  12. Lemaître-Coelho I., Jackson G. D., Vaerman J. P. High levels of secretory IgA and free secretory component in the serum of rats with bile duct obstruction. J Exp Med. 1978 Mar 1;147(3):934–939. doi: 10.1084/jem.147.3.934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McCoy R. C., Abramowsky C. R., Tisher C. C. IgA nephropathy. Am J Pathol. 1974 Jul;76(1):123–144. [PMC free article] [PubMed] [Google Scholar]
  14. McWilliams M., Lamm M. E., Phillips-Quagliata J. M. Surface and intracellular markers of mouse mesenteric and peripheral lymph node and Peyer's patch cells. J Immunol. 1974 Oct;113(4):1326–1333. [PubMed] [Google Scholar]
  15. Montgomery P. C., Lemaître-Coelho I. M., Vaerman J. P. Molecular diversity of secretory IgA anti-DNP antibodies elicited in rat bile. J Immunol. 1980 Aug;125(2):518–522. [PubMed] [Google Scholar]
  16. Nochy D., Callard P., Bellon B., Bariety J., Druet P. Association of overt glomerulonephritis and liver disease: a study of 34 patients. Clin Nephrol. 1976 Oct;6(4):422–427. [PubMed] [Google Scholar]
  17. Peppard J., Orlans E., Payne A. W., Andrew E. The elimination of circulating complexes containing polymeric IgA by excretion in the bile. Immunology. 1981 Jan;42(1):83–89. [PMC free article] [PubMed] [Google Scholar]
  18. Pfaffenbach G., Lamm M. E., Gigli I. Activation of the guinea pig alternative complement pathway by mouse IgA immune complexes. J Exp Med. 1982 Jan 1;155(1):231–247. doi: 10.1084/jem.155.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rifai A., Small P. A., Jr, Teague P. O., Ayoub E. M. Experimental IgA nephropathy. J Exp Med. 1979 Nov 1;150(5):1161–1173. doi: 10.1084/jem.150.5.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shirai T., Tomino Y., Sato M., Yoshiki T., Itoh T. IgA nephropathy: clinicopathology and immunopathology. Contrib Nephrol. 1978;9:88–100. doi: 10.1159/000401436. [DOI] [PubMed] [Google Scholar]
  21. Socken D. J., Simms E. S., Nagy B. R., Fisher M. M., Underdown B. J. Secretory component-dependent hepatic transport of IgA antibody-antigen complexes. J Immunol. 1981 Jul;127(1):316–319. [PubMed] [Google Scholar]
  22. Whitworth J. A., Leibowitz S., Kennedy M. C., Cameron J. S., Chantler C. IgA and glomerular disease. Clin Nephrol. 1976 Jan;5(1):33–36. [PubMed] [Google Scholar]
  23. Woodroffe A. J., Gormly A. A., McKenzie P. E., Wootton A. M., Thompson A. J., Seymour A. E., Clarkson A. R. Immunologic studies in IgA nephropathy. Kidney Int. 1980 Sep;18(3):366–374. doi: 10.1038/ki.1980.147. [DOI] [PubMed] [Google Scholar]

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