Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features

Semin Immunol. 2006 Dec;18(6):347-61. doi: 10.1016/j.smim.2006.07.010. Epub 2006 Sep 25.


Mendelian susceptibility to mycobacterial diseases confers predisposition to clinical disease caused by weakly virulent mycobacterial species in otherwise healthy individuals. Since 1996, disease-causing mutations have been found in five autosomal genes (IFNGR1, IFNGR2, STAT1, IL12B, IL12BR1) and one X-linked gene (NEMO). These genes display a high degree of allelic heterogeneity, defining at least 13 disorders. Although genetically different, these conditions are immunologically related, as all result in impaired IL-12/23-IFN-gamma-mediated immunity. These disorders were initially thought to be rare, but have now been diagnosed in over 220 patients from over 43 countries worldwide. We review here the molecular, cellular, and clinical features of patients with inborn errors of the IL-12/23-IFN-gamma circuit.

Publication types

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

MeSH terms

  • Animals
  • Genetic Diseases, Inborn / immunology*
  • Humans
  • Interferon-gamma / genetics*
  • Interferon-gamma / immunology
  • Interleukin-12 / genetics*
  • Interleukin-12 / immunology
  • Interleukin-23 / genetics*
  • Interleukin-23 / immunology
  • Mutation


  • Interleukin-23
  • Interleukin-12
  • Interferon-gamma