Selective insufficiency of IFN‐γ secretion in patients with hyper‐IgE syndrome

Background: Hyper-immunoglobulin E (IgE) syndrome is a complex immune deficiency characterized by chronic eczematous dermatitis, recurrent staphylococcal infections, pneumatoceles, reduced neutrophil chemotaxis, and variably impaired T cell function. Although decreased interferon-γ (IFN-γ) production in patients with hyper-IgE syndrome is pointed out and known as a cause of reduced neutrophil chemotaxis, precise mechanism of their inadequate production of IFN-γ remains unknown. To elucidate the pathogenesis of the defective production of IFN-γ in patients with hyper-IgE syndrome, we assessed the in vitro production and secretion of IFN-γ by peripheral blood mononuclear cells (PBMCs) from patients with hyper-IgE syndrome. Methods: Chemotaxis of neutrophils, mRNA levels of several cytokines, intracellular production and extracellular secretion of IFN-γ, interleukin-2 (IL-2), and IL-4 by PBMCs from three patients with hyper-IgE syndrome were determined. Results: The transcription of IFN-γ mRNA and the production of its protein molecules progressed normally. However, selective insufficiency in the secretion of IFN-γ molecules was found in patients with hyper-IgE syndrome.Confocal laser scanning microscopy clearly demonstrated the accumulation of IFN-γ in patients with hyper-IgE syndrome. Conclusion: We demonstrated that there was a selective insufficiency in the secretion of IFN-γ in patients with hyper-IgE syndrome. We hope that this fact would offer a new paradigm for understanding this disease.