Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 May;96(2):311–316. doi: 10.1111/j.1365-2249.1994.tb06559.x

Profiles of immunoregulatory cytokine production in vitro in patients with IgA nephropathy and their kindred.

V Scivittaro 1, L Gesualdo 1, E Ranieri 1, C Marfella 1, S A Schewn 1, S N Emancipator 1, F P Schena 1
PMCID: PMC1534876  PMID: 8187339

Abstract

We hypothesized that the altered immunoglobulin synthesis and/or lymphocyte function apparent in patients with IgA nephropathy (IgAN) is due to a primary defect in lymphokine regulation. In addition, we reasoned that such changes in lymphokine production might be, at least partially, genetically determined. To assess the extent of lymphocyte abnormalities, we investigated the profile of cytokine production from peripheral blood mononuclear cells (PBMC) in 34 IgAN patients and 44 of their first degree relatives, 10 of whom had persistent microhaematuria. Compared with healthy volunteers (n = 34), PBMC from patients showed increased IL-2 production both spontaneously or after phytohaemagglutinin (PHA) (20 micrograms/ml) stimulation, whereas IL-4 and interferon-gamma (IFN-gamma) production were significantly higher only after stimulation. Microhaematuric relatives had a similar pattern of cytokine production, whereas non-microhaematuric relatives showed no significant difference versus normals. The altered pattern of cytokine production appeared to be quite specific to IgAN patients and their microhaematuric relatives, because patients with other forms of primary glomerulonephritis (n = 17) did not differ from normal individuals. Patients and relatives that hyperproduced IL-4 were also hyperproducers of IL-2. No such congruence was seen in any other group or with any other pairing of cytokines. We propose that a subpopulation of IgAN patients bear lymphocytes intrinsically hyperresponsive. Among those individuals such hyperresponsiveness may be causally related to the pathogenesis and/or character of IgAN.

Full text

PDF
311

Selected References

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

  1. Clarkson A. R., Seymour A. E., Thompson A. J., Haynes W. D., Chan Y. L., Jackson B. IgA nephropathy: a syndrome of uniform morphology, diverse clinical features and uncertain prognosis. Clin Nephrol. 1977 Nov;8(5):459–471. [PubMed] [Google Scholar]
  2. D'Amico G., Imbasciati E., Barbiano Di Belgioioso G., Bertoli S., Fogazzi G., Ferrario F., Fellin G., Ragni A., Colasanti G., Minetti L. Idiopathic IgA mesangial nephropathy. Clinical and histological study of 374 patients. Medicine (Baltimore) 1985 Jan;64(1):49–60. [PubMed] [Google Scholar]
  3. Egido J., Blasco R. A., Sancho J., Hernando L. Immunological abnormalities in healthy relatives of patients with IgA nephropathy. Am J Nephrol. 1985;5(1):14–20. doi: 10.1159/000166897. [DOI] [PubMed] [Google Scholar]
  4. Emancipator S. N. Immunoregulatory factors in the pathogenesis of IgA nephropathy. Kidney Int. 1990 Dec;38(6):1216–1229. doi: 10.1038/ki.1990.337. [DOI] [PubMed] [Google Scholar]
  5. Emancipator S. N., Lamm M. E. IgA nephropathy: pathogenesis of the most common form of glomerulonephritis. Lab Invest. 1989 Feb;60(2):168–183. [PubMed] [Google Scholar]
  6. Emancipator S. N., Ovary Z., Lamm M. E. The role of mesangial complement in the hematuria of experimental IgA nephropathy. Lab Invest. 1987 Sep;57(3):269–276. [PubMed] [Google Scholar]
  7. Gesualdo L., Lamm M. E., Emancipator S. N. Defective oral tolerance promotes nephritogenesis in experimental IgA nephropathy induced by oral immunization. J Immunol. 1990 Dec 1;145(11):3684–3691. [PubMed] [Google Scholar]
  8. Jackson S., Galla J. H., Kirk K. A., Thorn B. T., Julian B. A. Epstein-Barr virus transformation of B lymphocytes from IgA nephropathy patients and first-degree relatives results in increased immunoglobulin synthesis not restricted to IgA. Am J Kidney Dis. 1991 Jan;17(1):55–61. doi: 10.1016/s0272-6386(12)80251-4. [DOI] [PubMed] [Google Scholar]
  9. Jennette J. C., Wall S. D., Wilkman A. S. Low incidence of IgA nephropathy in blacks. Kidney Int. 1985 Dec;28(6):944–950. doi: 10.1038/ki.1985.222. [DOI] [PubMed] [Google Scholar]
  10. Julian B. A., Quiggins P. A., Thompson J. S., Woodford S. Y., Gleason K., Wyatt R. J. Familial IgA nephropathy. Evidence of an inherited mechanism of disease. N Engl J Med. 1985 Jan 24;312(4):202–208. doi: 10.1056/NEJM198501243120403. [DOI] [PubMed] [Google Scholar]
  11. Julian B. A., Woodford S. Y., Baehler R. W., McMorrow R. G., Wyatt R. J. Familial clustering and immunogenetic aspects of IgA nephropathy. Am J Kidney Dis. 1988 Nov;12(5):366–370. doi: 10.1016/s0272-6386(88)80026-x. [DOI] [PubMed] [Google Scholar]
  12. Lai K. N., Leung J. C., Lai F. M., Tam J. S. T-lymphocyte activation in IgA nephropathy: serum-soluble interleukin 2 receptor level, interleukin 2 production, and interleukin 2 receptor expression by cultured lymphocytes. J Clin Immunol. 1989 Nov;9(6):485–492. doi: 10.1007/BF00918018. [DOI] [PubMed] [Google Scholar]
  13. Lai K. N., Leung J. C., Li P. K., Lui S. F. Cytokine production by peripheral blood mononuclear cells in IgA nephropathy. Clin Exp Immunol. 1991 Aug;85(2):240–245. doi: 10.1111/j.1365-2249.1991.tb05712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mosmann T. R., Moore K. W. The role of IL-10 in crossregulation of TH1 and TH2 responses. Immunol Today. 1991 Mar;12(3):A49–A53. doi: 10.1016/S0167-5699(05)80015-5. [DOI] [PubMed] [Google Scholar]
  15. Ohta K., Takano N., Seno A., Yachie A., Miyawaki T., Yokoyama H., Tomosugi N., Kato E., Taniguchi N. Detection and clinical usefulness of urinary interleukin-6 in the diseases of the kidney and the urinary tract. Clin Nephrol. 1992 Oct;38(4):185–189. [PubMed] [Google Scholar]
  16. Paliard X., de Waal Malefijt R., Yssel H., Blanchard D., Chrétien I., Abrams J., de Vries J., Spits H. Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. J Immunol. 1988 Aug 1;141(3):849–855. [PubMed] [Google Scholar]
  17. Parera M., Rivera F., Egido J., Campos A. The role of interleukin 2 (IL-2) and serum-soluble IL-2 receptor cells in idiopathic IgA nephropathy. Clin Immunol Immunopathol. 1992 May;63(2):196–199. doi: 10.1016/0090-1229(92)90013-e. [DOI] [PubMed] [Google Scholar]
  18. Romagnani S. Human TH1 and TH2 subsets: doubt no more. Immunol Today. 1991 Aug;12(8):256–257. doi: 10.1016/0167-5699(91)90120-I. [DOI] [PubMed] [Google Scholar]
  19. Sakai H., Nomoto Y., Arimori S., Komori K., Inouye H., Tsuji K. Increase of IgA-bearing peripheral blood lymphocytes in families of patients with IgA nephropathy. Am J Clin Pathol. 1979 Sep;72(3):452–456. doi: 10.1093/ajcp/72.3.452. [DOI] [PubMed] [Google Scholar]
  20. Sakai H. T-cell function. Contrib Nephrol. 1984;40:124–129. doi: 10.1159/000409739. [DOI] [PubMed] [Google Scholar]
  21. Schena F. P. A retrospective analysis of the natural history of primary IgA nephropathy worldwide. Am J Med. 1990 Aug;89(2):209–215. doi: 10.1016/0002-9343(90)90300-3. [DOI] [PubMed] [Google Scholar]
  22. Schena F. P., Mastrolitti G., Jirillo E., Munno I., Pellegrino N., Fracasso A. R., Aventaggiato L. Increased production of interleukin-2 and IL-2 receptor in primary IgA nephropathy. Kidney Int. 1989 Mar;35(3):875–879. doi: 10.1038/ki.1989.67. [DOI] [PubMed] [Google Scholar]
  23. Schena F. P., Scivittaro V., Ranieri E., Sinico R., Benuzzi S., Di Cillo M., Aventaggiato L. Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy. Clin Exp Immunol. 1993 Apr;92(1):139–144. doi: 10.1111/j.1365-2249.1993.tb05960.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Smith S. M., Tung K. S. Incidence of IgA-related nephritides in American Indians in New Mexico. Hum Pathol. 1985 Feb;16(2):181–184. doi: 10.1016/s0046-8177(85)80067-8. [DOI] [PubMed] [Google Scholar]
  25. Snapper C. M., Mond J. J. Towards a comprehensive view of immunoglobulin class switching. Immunol Today. 1993 Jan;14(1):15–17. doi: 10.1016/0167-5699(93)90318-F. [DOI] [PubMed] [Google Scholar]
  26. Waldo F. B., Beischel L., West C. D. IgA synthesis by lymphocytes from patients with IgA nephropathy and their relatives. Kidney Int. 1986 Jun;29(6):1229–1233. doi: 10.1038/ki.1986.132. [DOI] [PubMed] [Google Scholar]
  27. Yano N., Endoh M., Miyazaki M., Yamauchi F., Nomoto Y., Sakai H. Altered production of IgE and IgA induced by IL-4 in peripheral blood mononuclear cells from patients with IgA nephropathy. Clin Exp Immunol. 1992 May;88(2):295–300. doi: 10.1111/j.1365-2249.1992.tb03076.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yano N., Miyazaki M., Endoh M., Kuramoto T., Eguchi K., Yagame M., Nomoto Y., Sakai H. Increase of CD23-positive cells in peripheral blood from patients with IgA nephropathy and non-IgA proliferative glomerulonephritis. Nephron. 1992;60(4):404–410. doi: 10.1159/000186799. [DOI] [PubMed] [Google Scholar]
  29. Yokoyama H., Takaeda M., Wada T., Ogi M., Tomosugi N., Takabatake T., Abe T., Yoshimura M., Kida H., Kobayashi K. Intraglomerular expression of MHC class II and Ki-67 antigens and serum gamma-interferon levels in IgA nephropathy. Nephron. 1992;62(2):169–175. doi: 10.1159/000187028. [DOI] [PubMed] [Google Scholar]
  30. van den Wall Bake A. W., Crowley-Nowick P. A., Kulhavy R., Hermans J., Jackson S., Julian B. A., Mestecky J. Cytokine-induced immunoglobulin production in primary IgA nephropathy. Am J Kidney Dis. 1992 Dec;20(6):611–617. doi: 10.1016/s0272-6386(12)70228-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES