Defective interleukin-12/interferon-gamma pathway in patients with hyperimmunoglobulinemia E syndrome

J Pediatr. 2000 Feb;136(2):176-80. doi: 10.1016/s0022-3476(00)70098-9.


Objective: Patients with the hyperimmunoglobulinemia E (hyper-IgE) syndrome are reported to have defective production of interferon gamma (IFN-gamma). Because IFN-gamma is a major activator of polymorphonuclear leukocytes (PMNs), this could result in defective PMN chemotaxis and markedly elevated IgE levels because of the unopposed action of interleukin (IL)-4. IL-12, an important enhancer of IFN-gamma production, also suppresses IgE production. This study assessed the IL-12/IFN-gamma pathway in patients with hyper-IgE syndrome.

Methods: Production of IL-12 and IFN-gamma by mononuclear cells from 10 patients with hyper-IgE syndrome in response to a number of stimuli was determined, as well as the effect of IL-12 on IFN-gamma release and cell proliferation.

Results: IL-12 and IFN-gamma production by the patients' cells was similar to that of control subjects independent of the stimulus used, except for Staphylococcus aureus, with which cells of patients with hyper-IgE syndrome released markedly less IFN-gamma (19.8%; P <.002). The ability of recombinant IL-12 to enhance IFN-gamma release from patients' cells in response to all stimuli was, however, significantly lower than with control cells (12% to 51%; P <.03).

Conclusion: The lymphocytes of patients with hyper-IgE syndrome have an impaired response to IL-12, resulting in decreased IFN-gamma production, which may be of key importance in the pathogenesis of the immune abnormalities of hyper-IgE syndrome.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Candida albicans / immunology
  • Cells, Cultured
  • Child
  • Female
  • Humans
  • Immunoglobulin E / metabolism
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / physiology*
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / physiology*
  • Job Syndrome / genetics
  • Job Syndrome / immunology*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Staphylococcus aureus / immunology


  • Interleukin-12
  • Immunoglobulin E
  • Interferon-gamma