Hyper-IgE syndrome

Curr Opin Immunol. 2009 Oct;21(5):487-92. doi: 10.1016/j.coi.2009.07.013. Epub 2009 Aug 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Infections / complications
  • Cytokines / metabolism
  • Humans
  • Job Syndrome / etiology
  • Job Syndrome / genetics*
  • Job Syndrome / pathology
  • Models, Biological
  • Mutation*
  • STAT3 Transcription Factor / genetics*
  • Signal Transduction
  • TYK2 Kinase / genetics*
  • Virus Diseases / complications


  • Cytokines
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TYK2 Kinase
  • TYK2 protein, human