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 (PM Ns), this could result in defective PMN chemotaxis and markedly elevated Ig E levels because of the unopposed action of interleukin (IL)-4. IL-12, an i mportant 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 pat ients with hyper-IgE syndrome in response to a number of stimuli was determ ined, as well as the effect of IL-12 on IFN-gamma release and cell prolifer ation. 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 St aphylococcus aureus, with which cells of patients with hyper-IgE syndrome r eleased markedly less IFN-gamma (19.8%; P < .002). The ability of recombina nt IL-12 to enhance IFN-gamma release fr om 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 imp aired response to IL-12, resulting in decreased IFN-gamma production, which may be of key importance in the pathogenesis of the immune abnormalities o f hyper-IgE syndrome.