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


CONCLUSIONS
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.
Borges
W G
WG
Departments of Pathology, Pediatrics, and Medicine, University of Utah School of Medicine, and the ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84132, USA.
Augustine
N H
NH
Hill
H R
HR
D000293:Adolescent; D000328:Adult; D002176:Candida albicans / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology*; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D013211:Staphylococcus aureus / Q000276:immunology
D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma