Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Dec;86(24):10085–10089. doi: 10.1073/pnas.86.24.10085

Regulation of immunoglobulin production in hyperimmunoglobulin E recurrent-infection syndrome by interferon gamma.

C L King 1, J I Gallin 1, H L Malech 1, S L Abramson 1, T B Nutman 1
PMCID: PMC298649  PMID: 2513574

Abstract

The hyperimmunoglobulin E recurrent-infection (Job) syndrome (HIE) is a congenital disorder characterized by high serum IgE, chronic eczematoid dermatitis, and recurrent infections. We examined the effect of interferon gamma (IFN-gamma) on excessive IgE production in HIE patients. Spontaneous in vitro production of IgE by peripheral blood mononuclear cells from HIE patients was elevated compared to normal individuals and correlated with serum IgE. In 9 of 13 patients, IgE production by peripheral blood mononuclear cells was inhibited by 50% by IFN-gamma at 100-1000 units/ml, whereas inhibition by IFN-gamma at 10(4) units/ml ranged from 67 to 93% for these 9 patients. IFN-gamma also inhibited IgG1, IgG3, and IgG4 production by B lymphocytes without inhibiting IgG2 production. IFN-gamma was administered subcutaneously to 5 HIE patients. After 2 weeks of treatment with IFN-gamma (0.05 mg/m2) at three doses per week given on alternate days, peripheral blood mononuclear cells from all 5 HIE patients decreased spontaneous in vitro IgE production (27-62% decrease) with no change in IgG and IgM. One patient had a 58% decrease in serum IgE and another patient had a 50% decrease in serum IgE after the IFN-gamma was increased to 0.1 mg/m2 for three doses per week for a month. In both patients, serum IgE returned to pre-IFN-gamma-challenge levels 1-3 months after completion of treatment, and in vivo IFN-gamma did not affect serum IgG and IgM, although serum IgG4 decreased with changes in serum IgE. Our studies demonstrate that IFN-gamma can regulate production of IgE and some IgG subclasses in humans.

Full text

PDF
10085

Images in this article

Selected References

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

  1. Coffman R. L., Carty J. A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol. 1986 Feb 1;136(3):949–954. [PubMed] [Google Scholar]
  2. Coffman R. L., Ohara J., Bond M. W., Carty J., Zlotnik A., Paul W. E. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol. 1986 Jun 15;136(12):4538–4541. [PubMed] [Google Scholar]
  3. Coffman R. L., Seymour B. W., Lebman D. A., Hiraki D. D., Christiansen J. A., Shrader B., Cherwinski H. M., Savelkoul H. F., Finkelman F. D., Bond M. W. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988 Feb;102:5–28. doi: 10.1111/j.1600-065x.1988.tb00739.x. [DOI] [PubMed] [Google Scholar]
  4. Deguchi H., Suemura M., Ishizaka A., Ozaki Y., Kishimoto S., Yamamura Y., Kishimoto T. IgE class-specific suppressor T cells and factors in humans. J Immunol. 1983 Dec;131(6):2751–2756. [PubMed] [Google Scholar]
  5. Del Prete G., Maggi E., Parronchi P., Chrétien I., Tiri A., Macchia D., Ricci M., Banchereau J., De Vries J., Romagnani S. IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J Immunol. 1988 Jun 15;140(12):4193–4198. [PubMed] [Google Scholar]
  6. Donabedian H., Gallin J. I. The hyperimmunoglobulin E recurrent-infection (Job's) syndrome. A review of the NIH experience and the literature. Medicine (Baltimore) 1983 Jul;62(4):195–208. doi: 10.1097/00005792-198307000-00001. [DOI] [PubMed] [Google Scholar]
  7. Ezekowitz R. A., Dinauer M. C., Jaffe H. S., Orkin S. H., Newburger P. E. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med. 1988 Jul 21;319(3):146–151. doi: 10.1056/NEJM198807213190305. [DOI] [PubMed] [Google Scholar]
  8. Finkelman F. D., Katona I. M., Mosmann T. R., Coffman R. L. IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol. 1988 Feb 15;140(4):1022–1027. [PubMed] [Google Scholar]
  9. Geha R. S. Regulation of IgE synthesis in atopic disease. Hosp Pract (Off Ed) 1988 Feb 15;23(2):91–102. doi: 10.1080/21548331.1988.11703417. [DOI] [PubMed] [Google Scholar]
  10. Hassner A., Saxon A. Inhibition of ongoing myeloma IgE synthesis in vitro by activated human T cells. J Immunol. 1983 Apr;130(4):1567–1572. [PubMed] [Google Scholar]
  11. Hussain R., Poindexter R. W., Wistar R., Reimer C. B. Use of monoclonal antibodies to quantify subclasses of human IgG. I. Development of two-site immunoenzymometric assays for total IgG subclass determinations. J Immunol Methods. 1986 Oct 23;93(1):89–96. doi: 10.1016/0022-1759(86)90437-0. [DOI] [PubMed] [Google Scholar]
  12. Ishizaka K. Regulation of IgE synthesis. Annu Rev Immunol. 1984;2:159–182. doi: 10.1146/annurev.iy.02.040184.001111. [DOI] [PubMed] [Google Scholar]
  13. Kirchner S. G., Sivit C. J., Wright P. F. Hyperimmunoglobulinemia E syndrome: association with osteoporosis and recurrent fractures. Radiology. 1985 Aug;156(2):362–362. doi: 10.1148/radiology.156.2.4011897. [DOI] [PubMed] [Google Scholar]
  14. Kurzrock R., Quesada J. R., Talpaz M., Hersh E. M., Reuben J. M., Sherwin S. A., Gutterman J. U. Phase I study of multiple dose intramuscularly administered recombinant gamma interferon. J Clin Oncol. 1986 Jul;4(7):1101–1109. doi: 10.1200/JCO.1986.4.7.1101. [DOI] [PubMed] [Google Scholar]
  15. Leung D. Y., Brozek C., Frankel R., Geha R. S. IgE-specific suppressor factors in normal human serum. Clin Immunol Immunopathol. 1984 Sep;32(3):339–350. doi: 10.1016/0090-1229(84)90277-0. [DOI] [PubMed] [Google Scholar]
  16. Leung D. Y., Geha R. S. Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome. Hematol Oncol Clin North Am. 1988 Mar;2(1):81–100. [PubMed] [Google Scholar]
  17. Leung D. Y., Young M. C., Wood N., Geha R. S. Induction of IgE synthesis in normal human B cells. Sequential requirements for activation by an alloreactive T cell clone and IgE-potentiating factors. J Exp Med. 1986 Mar 1;163(3):713–723. doi: 10.1084/jem.163.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nutman T. B., Delespesse G., Sarfati M., Volkman D. J. T-cell-derived IgE-binding factors. I. Cloned and transformed T cells producing IgE-binding factors. J Immunol. 1987 Dec 15;139(12):4049–4054. [PubMed] [Google Scholar]
  19. Nutman T. B., Hussain R., Ottesen E. A. IgE production in vitro by peripheral blood mononuclear cells of patients with parasitic helminth infections. Clin Exp Immunol. 1984 Oct;58(1):174–182. [PMC free article] [PubMed] [Google Scholar]
  20. Nutman T. B., Volkman D. J., Hussain R., Fauci A. S., Ottesen E. A. Filarial parasite-specific T cell lines: induction of IgE synthesis. J Immunol. 1985 Feb;134(2):1178–1184. [PubMed] [Google Scholar]
  21. Ottesen E. A., Skvaril F., Tripathy S. P., Poindexter R. W., Hussain R. Prominence of IgG4 in the IgG antibody response to human filariasis. J Immunol. 1985 Apr;134(4):2707–2712. [PubMed] [Google Scholar]
  22. Parkin J. M., Eales L. J., Galazka A. R., Pinching A. J. Atopic manifestations in the acquired immune deficiency syndrome: response to recombinant interferon gamma. Br Med J (Clin Res Ed) 1987 May 9;294(6581):1185–1186. doi: 10.1136/bmj.294.6581.1185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rabin E. M., Mond J. J., Ohara J., Paul W. E. Interferon-gamma inhibits the action of B cell stimulatory factor (BSF)-1 on resting B cells. J Immunol. 1986 Sep 1;137(5):1573–1576. [PubMed] [Google Scholar]
  24. Romagnani S., Maggi E., Del Prete G. F., Ricci M. IgE synthesis in vitro induced by T cell factors from patients with elevated serum IgE levels. Clin Exp Immunol. 1983 Apr;52(1):85–88. [PMC free article] [PubMed] [Google Scholar]
  25. Saryan J. A., Leung D. Y., Geha R. S. Induction of human IgE synthesis by a factor derived from T cells of patients with hyper-IgE states. J Immunol. 1983 Jan;130(1):242–247. [PubMed] [Google Scholar]
  26. Saryan J. A., Rappeport J., Leung D. Y., Parkman R., Geha R. S. Regulation of human immunoglobulin E synthesis in acute graft versus host disease. J Clin Invest. 1983 Mar;71(3):556–564. doi: 10.1172/JCI110800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saxon A., Morrow C., Stevens R. H. Subpopulations of circulating B cells and regulatory T cells involved in in vitro immunoglobulin E production in atopic patients with elevted serum immunoglobulin E. J Clin Invest. 1980 Jun;65(6):1457–1468. doi: 10.1172/JCI109810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sechler J. M., Malech H. L., White C. J., Gallin J. I. Recombinant human interferon-gamma reconstitutes defective phagocyte function in patients with chronic granulomatous disease of childhood. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4874–4878. doi: 10.1073/pnas.85.13.4874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sherr E. H., Stein L. D., Dosch H. M., Saxon A. IgE-enhancing activity directly and selectively affects activated B cells: evidence for a human IgE differentiation factor. J Immunol. 1987 Jun 1;138(11):3836–3843. [PubMed] [Google Scholar]
  30. Snapper C. M., Paul W. E. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. doi: 10.1126/science.3107127. [DOI] [PubMed] [Google Scholar]
  31. Umetsu D. T., Leung D. Y., Siraganian R., Jabara H. H., Geha R. S. Differential requirements of B cells from normal and allergic subjects for the induction of IgE synthesis by an alloreactive T cell clone. J Exp Med. 1985 Jul 1;162(1):202–214. doi: 10.1084/jem.162.1.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vercelli D., Geha R. S. Regulation of IgE synthesis in humans. J Clin Immunol. 1989 Mar;9(2):75–83. doi: 10.1007/BF00916934. [DOI] [PubMed] [Google Scholar]
  33. Young M. C., Leung D. Y., Geha R. S. Production of IgE-potentiating factor in man by T cell lines bearing Fc receptors for IgE. Eur J Immunol. 1984 Oct;14(10):871–878. doi: 10.1002/eji.1830141003. [DOI] [PubMed] [Google Scholar]
  34. Zuraw B. L., Nonaka M., O'Hair C., Katz D. H. Human IgE antibody synthesis in vitro: stimulation of IgE responses by pokeweed mitogen and selective inhibition of such responses by human suppressive factor of allergy (SFA). J Immunol. 1981 Sep;127(3):1169–1177. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES