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

Abstract

Objective: Patients with the hyperimmunoglobulinemia E (hyper-IgE) syndrome are reported to have defective production of interferon gamma (IFN-γ). Because IFN-γ 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-γ production, also suppresses IgE production. This study assessed the IL-12/IFN-γ pathway in patients with hyper-IgE syndrome. Methods: Production of IL-12 and IFN-γ 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-γ release and cell proliferation. Results: IL-12 and IFN-γ 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-γ (19.8%; P < .002). The ability of recombinant IL-12 to enhance IFN-γ 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-γ production, which may be of key importance in the pathogenesis of the immune abnormalities of hyper-IgE syndrome. (J Pediatr 2000;136:176-80.)