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

Abstract

The hyperimmunoglobulin E recurrent-infection (Job) syndrome (HIE) is a congenital disorder characterized by high serum IgE, chronic eczematoid dermatitis, and recurrent infections. We examined the effect of interferon Y (IFN-y) 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-y at 100-1000 units/ml, whereas inhibition by IFN-y at 104 units/ml ranged from 67 to 93% for these 9 patients. IFN-y also inhibited IgG1, IgG3, and IgG4 production by B lymphocytes without inhibiting IgG2 production. IFN-y was administered subcutaneously to 5 HIE patients. After 2 weeks of treatment with IFN-y (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-y was increased to 0.1 mg/M2 for three doses per week for a month. In both patients, serum IgE returned to pre-IFN-y-challenge levels 1-3 months after completion of treatment, and in vivo IFN-y did not affect serum IgG and IgM, although serum IgG4 decreased with changes in serum IgE. Our studies demonstrate that IFN-y can regulate production of IgE and some IgG subclasses in humans.

Inhibition of T helper 2‐type responses, IgE production and eosinophilia by synthetic lipopeptides

“…Several studies have demonstrated the IgE inhibitory effects of IL-10, IL-12 and IFN-+ [7,28]. In addition, IFN-+ was successfully used to treat hyper-IgE patients [29]. Consistent with this, the present study demonstrates that LP40 inhibits IgE in several mice models.…”

Bone marrow transplantation does not correct the hyper IgE syndrome

“…1 Although the primary immunological defect in HIE has remained elusive, recent findings indicate a profound impairment in the regulation of interleukin 4 (IL-4)-dependent IgE production, 2 confirming previously published data showing defective interferon gamma (IFN␥) production. 3 This pattern, however, seems not to be specific as it has been shown in chronic mucocutaneous candidiasis, 4 another rare primary immunodeficiency of unknown aetiology. The mainstay of conventional management in HIE is aggressive antibiotic treatment and prophylaxis targeting Staphylococcus aureus, the known main pathogen in these patients.…”

“…The mainstay of conventional management in HIE is aggressive antibiotic treatment and prophylaxis targeting Staphylococcus aureus, the known main pathogen in these patients. Both IFN␥ 3 and cyclosporin A (CsA) 5 have been tried as supplementary agents, but no treatment is curative. We present the case of a child with severe HIE in whom bone marrow transplantation (BMT) was performed in the expectation that at least the immunological defect would be cured by replacing the pluripotent haematopoietic stem cells.…”

Anestesia em paciente com Síndrome de Jó (hiper IgE): Relato de caso

“…treatment with intravenous immunoglobulin an reduce the number and severity of recurring infections in some patients 16 . the use of in vitro gamma interferon showed improved neutrophil chemotaxis; however, in vivo it showed inconsistent effects on igE levels 17 .…”