Regulation of immunoglobulin production in hyperimmunoglobulin E recurrent-infection syndrome by interferon gamma.

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Abstract
The hyperimmunoglobulin E recurrent-infection (Job) syndrome (HIE) is a congenital disorder chararcterized by high serum IgE, chronic eczematoid dermatitis, and recurrent infections. We examined the effect of interferon .gamma. (IFN-.gamma.) on excessive IgE production in HIE patients. Spontaneous in vitro production of IgE by peripheral blood mononuclear cells from HIE patients was elevated compared to normal individuals and correlated with serum IgE. In 9 of 13 patients, IgE production by peripheral blood mononuclear cells was inhibited by 50% by IFN-.gamma. at 100-1000 units/ml, whereas inhibition by IFN-.gamma. at 104 units/ml ranged from 67 to 93% for these 9 patients. IFN-.gamma. also inhibited IgG1, IgG3, and IgG4 production by B lymphocytes without inhibiting IgG2 production. IFN-.gamma. was administered subcutaneously to 5 HIE patients. After 2 weeks of treatment with IFN-.gamma. (0.05 mg/m2) at three doses per week given on alternate days, peripheral blood mononuclear cells from all 5 HIE patients decreased spontaneous in vitro IgE production (27-62% decrease) with no change in IgG and IgM. One patient had a 58% decrease in serum IgE and another patient had a 50% decrease in serum IgE after the IFN-.gamma. was increased to 0.1 mg/m2 for three doses per week for a month. In both patients, serum IgE returned to pre-IFN-.gamma.-challenge levels 1-3 months after completion of treatment, and in vivo IFN-.gamma. did not affect serum IgG and IgM, although serum IgG4 decreased with changes in serum IgE. Our studies demonstrated that IFN-.gamma. can regulate production of IgE and some IgG subclasses in humans.