Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Jun;88(3):394–398. doi: 10.1111/j.1365-2249.1992.tb06460.x

Increased and prolonged production of specific polymeric IgA after systemic immunization with tetanus toxoid in IgA nephropathy.

L Layward 1, A C Allen 1, S J Harper 1, J M Hattersley 1, J Feehally 1
PMCID: PMC1554506  PMID: 1606721

Abstract

IgA nephropathy (IgAN) is a chronic form of glomerulonephritis which is characterized by the deposition in the glomerular mesangium of polymeric IgA (pIgA), the source of which is unknown. In order to investigate the production of pIgA in IgAN, patients were immunized systemically with tetanus toxoid (TT). Two weeks after immunization patients and controls responded to TT with an IgA response of similar magnitude. HPLC separation of sera showed that patients with IgAN produce significantly more pIgA anti-TT than controls (7.7 versus 2.88 arbitrary units; P less than 0.04). At this time, 33% of serum IgA anti-TT produced by patients with IgAN was polymeric, compared with 21% produced by controls (P less than 0.02). Monomeric IgA (mIgA) anti-TT levels were similar in both groups. Four weeks after immunization the proportion of pIgA anti-TT in controls and patients was significantly reduced from the 2 week level (from 21% to 0%, P less than 0.02 for controls; and from 33% to 8%, P less than 0.001, for patients). Only four out of 12 controls had any detectable pIgA anti-TT at this time compared with nine out of 10 patients with IgAN (P less than 0.05), and IgAN patients produced proportionally more pIgA anti-TT than did controls (median 8%, interquartile ranges (IQR) 4-10% versus 0% IQR 0-3%; P less than 0.01). HPLC analysis under acid conditions did not alter the pattern of pIgA and mIgA anti-TT, suggesting that the high molecular weight IgA fraction was not due to complexes. These data indicate that circulating pIgA results (at least in part) from a systemic response to antigen, which may be exaggerated in IgAN.

Full text

PDF
394

Selected References

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

  1. Alley C. D., Kiyono H., McGhee J. R. Murine bone marrow IgA responses to orally administered sheep erythrocytes. J Immunol. 1986 Jun 15;136(12):4414–4419. [PubMed] [Google Scholar]
  2. Andre P. M., Le Pogamp P., Chevet D. Impairment of jacalin binding to serum IgA in IgA nephropathy. J Clin Lab Anal. 1990;4(2):115–119. doi: 10.1002/jcla.1860040208. [DOI] [PubMed] [Google Scholar]
  3. Bene M. C., Faure G., Duheille J. IgA nephropathy: characterization of the polymeric nature of mesangial deposits by in vitro binding of free secretory component. Clin Exp Immunol. 1982 Mar;47(3):527–534. [PMC free article] [PubMed] [Google Scholar]
  4. Conley M. E., Cooper M. D., Michael A. F. Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus. J Clin Invest. 1980 Dec;66(6):1432–1436. doi: 10.1172/JCI109998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conley M. E., Delacroix D. L. Intravascular and mucosal immunoglobulin A: two separate but related systems of immune defense? Ann Intern Med. 1987 Jun;106(6):892–899. doi: 10.7326/0003-4819-106-6-892. [DOI] [PubMed] [Google Scholar]
  6. Czerkinsky C., Koopman W. J., Jackson S., Collins J. E., Crago S. S., Schrohenloher R. E., Julian B. A., Galla J. H., Mestecky J. Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangial immunoglobulin A nephropathies. J Clin Invest. 1986 Jun;77(6):1931–1938. doi: 10.1172/JCI112522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. D'Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 1987 Sep;64(245):709–727. [PubMed] [Google Scholar]
  8. Delacroix D. L., Elkom K. B., Geubel A. P., Hodgson H. F., Dive C., Vaerman J. P. Changes in size, subclass, and metabolic properties of serum immunoglobulin A in liver diseases and in other diseases with high serum immunoglobulin A. J Clin Invest. 1983 Feb;71(2):358–367. doi: 10.1172/JCI110777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Egido J., Blasco R., Sancho J., Lozano L., Sanchez-Crespo M., Hernando L. Increased rates of polymeric IgA synthesis by circulating lymphoid cells in IgA mesangial glomerulonephritis. Clin Exp Immunol. 1982 Feb;47(2):309–316. [PMC free article] [PubMed] [Google Scholar]
  10. Endoh M., Suga T., Miura M., Tomino Y., Nomoto Y., Sakai H. In vivo alteration of antibody production in patients with IgA nephropathy. Clin Exp Immunol. 1984 Sep;57(3):564–570. [PMC free article] [PubMed] [Google Scholar]
  11. Feehally J., Beattie T. J., Brenchley P. E., Coupes B. M., Mallick N. P., Postlethwaite R. J. Sequential study of the IgA system in relapsing IgA nephropathy. Kidney Int. 1986 Dec;30(6):924–931. doi: 10.1038/ki.1986.274. [DOI] [PubMed] [Google Scholar]
  12. Feehally J. Immune mechanisms in glomerular IgA deposition. Nephrol Dial Transplant. 1988;3(4):361–378. doi: 10.1093/oxfordjournals.ndt.a091683. [DOI] [PubMed] [Google Scholar]
  13. Jones C. L., Powell H. R., Kincaid-Smith P., Roberton D. M. Polymeric IgA and immune complex concentrations in IgA-related renal disease. Kidney Int. 1990 Aug;38(2):323–331. doi: 10.1038/ki.1990.204. [DOI] [PubMed] [Google Scholar]
  14. Kutteh W. H., Prince S. J., Mestecky J. Tissue origins of human polymeric and monomeric IgA. J Immunol. 1982 Feb;128(2):990–995. [PubMed] [Google Scholar]
  15. Leinikki P. O., Mustonen J., Pasternack A. Immune response to oral polio vaccine in patients with IgA glomerulonephritis. Clin Exp Immunol. 1987 Apr;68(1):33–38. [PMC free article] [PubMed] [Google Scholar]
  16. Lesavre P., Digeon M., Bach J. F. Analysis of circulating IgA and detection of immune complexes in primary IgA nephropathy. Clin Exp Immunol. 1982 Apr;48(1):61–69. [PMC free article] [PubMed] [Google Scholar]
  17. Lomax-Smith J. D., Zabrowarny L. A., Howarth G. S., Seymour A. E., Woodroffe A. J. The immunochemical characterization of mesangial IgA deposits. Am J Pathol. 1983 Dec;113(3):359–364. [PMC free article] [PubMed] [Google Scholar]
  18. Lozano L., García-Hoyo R., Egido J. IgA nephropathy: association of a history of macroscopic hematuria episodes with increased production of polymeric IgA. Nephron. 1987;45(2):98–103. doi: 10.1159/000184087. [DOI] [PubMed] [Google Scholar]
  19. Mascart-Lemone F., Duchateau J., Conley M. E., Delacroix D. L. A polymeric IgA response in serum can be produced by parenteral immunization. Immunology. 1987 Aug;61(4):409–413. [PMC free article] [PubMed] [Google Scholar]
  20. Monteiro R. C., Halbwachs-Mecarelli L., Roque-Barreira M. C., Noel L. H., Berger J., Lesavre P. Charge and size of mesangial IgA in IgA nephropathy. Kidney Int. 1985 Oct;28(4):666–671. doi: 10.1038/ki.1985.181. [DOI] [PubMed] [Google Scholar]
  21. Muso E., Yoshida H., Takeuchi E., Shimada T., Yashiro M., Sugiyama T., Kawai C. Pathogenic role of polyclonal and polymeric IgA in a murine model of mesangial proliferative glomerulonephritis with IgA deposition. Clin Exp Immunol. 1991 Jun;84(3):459–465. [PMC free article] [PubMed] [Google Scholar]
  22. Pasternack A., Mustonen J., Leinikki P. Humoral immune response in patients with IgA and IgM glomerulonephritis. Clin Exp Immunol. 1986 Jan;63(1):228–233. [PMC free article] [PubMed] [Google Scholar]
  23. Rifai A., Schena F. P., Montinaro V., Mele M., D'Addabbo A., Nitti L., Pezzullo J. C. Clearance kinetics and fate of macromolecular IgA in patients with IgA nephropathy. Lab Invest. 1989 Oct;61(4):381–388. [PubMed] [Google Scholar]
  24. Tomino Y., Sakai H., Miura M., Endoh M., Nomoto Y. Detection of polymeric IgA in glomeruli from patients with IgA nephropathy. Clin Exp Immunol. 1982 Aug;49(2):419–425. [PMC free article] [PubMed] [Google Scholar]
  25. van den Wall Bake A. W., Beyer W. E., Evers-Schouten J. H., Hermans J., Daha M. R., Masurel N., van Es L. A. Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy. An analysis of isotype distribution and size of the influenza-specific antibodies. J Clin Invest. 1989 Oct;84(4):1070–1075. doi: 10.1172/JCI114269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. van den Wall Bake A. W., Daha M. R., Radl J., Haaijman J. J., Van der Ark A., Valentijn R. M., Van Es L. A. The bone marrow as production site of the IgA deposited in the kidneys of patients with IgA nephropathy. Clin Exp Immunol. 1988 May;72(2):321–325. [PMC free article] [PubMed] [Google Scholar]
  27. van den Wall Bake A. W., Daha M. R., van der Ark A., Hiemstra P. S., Radl J., van Es L. A. Serum levels and in vitro production of IgA subclasses in patients with primary IgA nephropathy. Clin Exp Immunol. 1988 Oct;74(1):115–120. [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES