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.
Minegishi
Yoshiyuki
Y
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
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
D016207:Cytokines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053634:TYK2 Kinase; C070139:TYK2 protein, human