Background: Hyperimmunoglobulin E (hyper-IgE) syndrome is a rare immunodeficiency characterised by recurrent skin and respiratory tract infections, skeletal and dental abnormalities, chronic eczema, and elevated serum IgE. We describe a family with four hyper-IgE syndrome patients (38, 37, 30 and 7 years old), in which we investigated the cytokine response to both specific and non-specific stimulation.
Methods: Whole blood from patients and volunteers was stimulated for either 24 or 48h at 37 degrees C with heat-killed Staphylococcus, C. albicans or a combination of IL-12 and IL-18. Cytokine concentrations in the plasma were measured by specific radioimmuno-assays or ELISA.
Results: Serum IgE ranged from 5,000 to 16,670 IU/ml, and neutrophil chemotaxis was normal in all four patients. Tumour necrosis factor, interleukin (IL)-1beta, IL-6 and IL-8 production after stimulation of whole-blood cultures with lipopolysaccharide or heat-killed S. aureus did not differ between the adult patients and four healthy controls. In contrast, when blood from patients and controls was stimulated with heat-killed S. aureus or C. albicans, a severe imbalance towards a Th2 phenotype was found, with 10- to 30-fold reduction in the IFNgamma/IL-10 ratios in the hyper-IgE syndrome patients. The IFNgamma production in the patients was less severely impaired when blood was non-specifically stimulated with a combination of IL-18 and IL-12.
Conclusion: In this family with hyper-IgE syndrome, the imbalance in the Th1/Th2 cytokine production may have been involved in the pathogenesis of the recurrent infections and/or chronic eczema characteristic of this disease.