Inherited disorders of NF-kappaB-mediated immunity in man

Curr Opin Immunol. 2004 Feb;16(1):34-41. doi: 10.1016/j.coi.2003.11.013.


The transcription factors of the NF-kappaB family play an important role in immunity to infection in animal models. Three human primary immunodeficiencies associated with impaired NF-kappaB signaling were recently described. X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the gene encoding NEMO/IKKgamma, the regulatory subunit of the IkappaB-kinase (IKK) complex. Autosomal dominant EDA-ID (AD-EDA-ID) is caused by a hypermorphic mutation in the gene encoding the inhibitory protein IkappaBalpha. Autosomal recessive immunodeficiency without EDA is caused by mutations in the gene encoding IRAK-4, a kinase acting upstream from the IKK complex in the TIR signaling pathway. The description of the infectious phenotypes associated with these genetic defects has initiated the forward genetic dissection of NF-kappaB-mediated immunity in man.

Publication types

  • Review

MeSH terms

  • Animals
  • Ectodermal Dysplasia / genetics*
  • Ectodermal Dysplasia / immunology
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / immunology
  • Humans
  • I-kappa B Kinase
  • I-kappa B Proteins / genetics*
  • I-kappa B Proteins / metabolism
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Interleukin-1 Receptor-Associated Kinases
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Point Mutation
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction / immunology


  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • NF-KappaB Inhibitor alpha
  • Phosphotransferases (Alcohol Group Acceptor)
  • Interleukin-1 Receptor-Associated Kinases
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human