title: Rare mendelian primary immunodeficiency diseases associated with impaired NF-κB signaling.
abstract: Mendelian primary immunodeficiency diseases (MPIDs) are rare disorders affecting distinct constituents of the innate and adaptive immune system. Although they are genetically heterogeneous, a substantial group of MPIDs is due to mutations in genes affecting the nuclear factor-κB (NF-κB) transcription pathway, essential for cell proliferation and cell survival and involved in innate immunity and inflammation. Many of these genes encode for crucial regulatory components of the NF-κB pathway and their mutations are associated with immunological and developmental signs somehow overlapping in patients with MPIDs. At present, nine different MPIDs listed in the online mendelian inheritance in man (OMIM) are caused by mutations in at least nine different genes strictly involved in the NF-κB pathway that result in defects in immune responses. Here we report on the distinct function of each causative gene, on the impaired NF-κB step and more in general on the molecular mechanisms underlining the pathogenesis of the disease. Overall, the MPIDs affecting the NF-κB signalosome require a careful integrated diagnosis and appropriate genetic tests to be molecularly identified. Their discovery at an ever-increasing rate will help establish a common therapeutic strategy for a subclass of immunodeficient patients.
authors.affiliation: 1] Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', IGB-CNR, Naples, Italy [2] Department of Science, University of Basilicata, Potenza, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Paciolla
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', IGB-CNR, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pescatore
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', IGB-CNR, Naples, Italy.
authors.forename: M I
authors.initials: MI
authors.lastname: Conte
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', IGB-CNR, Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Fondazione SDN IRCCS, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Incoronato
authors.affiliation: Department of Science, University of Basilicata, Potenza, Italy.
authors.forename: M B
authors.initials: MB
authors.lastname: Lioi
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', IGB-CNR, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Fusco
authors.affiliation: 1] Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', IGB-CNR, Naples, Italy [2] Fondazione SDN IRCCS, Naples, Italy.
authors.forename: M V
authors.initials: MV
authors.lastname: Ursini
mesh_terms: D004476:Ectodermal Dysplasia / Q000235:genetics / Q000276:immunology; D005808:Genes, Recessive; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D000081207:Primary Immunodeficiency Diseases; D035583:Rare Diseases / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D016328:NF-kappa B; D053592:Interleukin-1 Receptor-Associated Kinases; D051550:I-kappa B Kinase; C496560:IKBKB protein, human