title: Hyper-IgE syndrome.
abstract: 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.
authors.affiliation: Department of Immune Regulation, Graduate School, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Yushima, Tokyo 113-8519, Japan. yminegishi.mbch@tmd.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Minegishi
mesh_terms: D001424:Bacterial Infections / Q000150:complications; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007589:Job Syndrome / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008954:Models, Biological; D009154:Mutation; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000235:genetics*; D014777:Virus Diseases / Q000150:complications
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053634:TYK2 Kinase; C070139:TYK2 protein, human