Rare Mendelian Primary Immunodeficiency diseases associated to impaired NF-κB signaling

• Published in: Genes and immunity Vol. 16; no. 4; pp. 239 - 246
• Main Authors: Paciolla, Mariateresa, Pescatore, Alessandra, Conte, Matilde Immacolata, Esposito, Elio, Incoronato, Mariarosaria, Lioi, Maria Brigida, Fusco, Francesca, Ursini, Matilde Valeria
• Format: Journal Article
• Language: English
• Published: 12.03.2015
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2015.3

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 NF-κB transcription pathway, essential for cell proliferation, cell survival, and involved in innate immunity and in inflammation. Many of these genes encode for crucial regulatory components of 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 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. We will report here 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 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 to establish common therapeutic strategy for a subclass of immunodeficient patients.