Hyper-IgE syndrome

Hyper-IgE syndrome (HIES) is a complex primary immunodeficiency characterized by atopic dermatitis associated with extremely high serum IgE levels and susceptibility to infections with extracellular bacteria. Nonimmunological abnormalities, including a distinctive facial appearance, fracture following minor trauma, scoliosis, hyperextensive joints, and the retention of deciduous teeth are also observed in most patients. Recent studies have demonstrated that dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) gene result in the classical multisystem form of HIES, whereas a null mutation in the tyrosine kinase 2 (Tyk2) gene causes an autosomal recessive HIES associated with viral and mycobacterial infections. In both patients, signal transduction for multiple cytokines, including IL-6 and IL-23, was defective, resulting in impaired T(H)17 function. These findings suggest that the defect in cytokine signaling constitutes the molecular basis for the immunological and nonimmunological abnormalities observed in HIES.