Abstract 38 Allergy, Immunology, and Rheumatology Poster Symposium, Sunday, 5/2
Patients with Job syndrome of hyperimmunoglobulinemia E and recurrent infections have been reported to have defective production of interferon-gamma (IFN[γ]). This could result in two of the most frequently described immune abnormalities in the syndrome, markedly elevated IgE due to the unopposed action of IL-4 and defective polymorphonuclear leukocyte (PMN) chemotaxis since IFN[γ] is a major activator of these cells. Interleukin 12 (IL-12) is one of the most important inducers of IFN[γ] production and also suppresses IgE production. In the present study, we examined the production of IL-12 and IFN[γ] by mononuclear cells from ten Job syndrome patients in response to a number of stimuli ([Staphylococcus aureus, Staphylococcus aureus] Cowan I strain, tetanus toxoid, tumor necrosis factor [α] and interleukin-2), as well as the effect of IL-12 on IFN[γ] release and proliferation of cells from these patients to determine if the IL-12/IFN[γ] pathway is intact. IL-12 and IFN[γ] production by the patients cells was similar to that of controls, independent of the stimulus employed, except with [S. aureus.] Job syndrome patients' cells released markedly less IFN[γ] (19.8%; p, 0.002) compared to cells from ten controls in response to [S. aureus.] The ability of recombinant IL-12 (rIL-12) to enhance IFN[γ] release from patients' cells in response to all stimuli was, however, significantly lower than with control cells (12-51%; p<0.03 to 0.001). These data indicate that the lymphocytes of Job syndrome patients have an impaired response to IL-12 resulting in decreased IFN[γ] production to a variety of stimuli. This abnormality may have a key role in the pathogenesis of the underlying immune abnormalities in Job syndrome.
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Borges, W., Augustine, N. & Hill, H. Defective IL-12/IFN-gamma Pathway in Patients with Job Syndrome of Hyperimmunoglobulin E and Recurrent Infections. Pediatr Res 45, 8 (1999). https://doi.org/10.1203/00006450-199904020-00055
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DOI: https://doi.org/10.1203/00006450-199904020-00055