title: Inherited disorders of NF-kappaB-mediated immunity in man.
abstract: 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.
authors.affiliation: Université de Paris René Descartes, Institut National de la Santé et de la Recherche Médicale U550, Faculté de Médecine Necker, 75015 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Cheng-Lung
authors.initials: CL
authors.lastname: Ku
authors.forename: Asma
authors.initials: A
authors.lastname: Smahi
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000818:Animals; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000276:immunology; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000235:genetics* / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D053592:Interleukin-1 Receptor-Associated Kinases; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D017853:Phosphotransferases (Alcohol Group Acceptor); D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human