Boisson, BertrandLaplantine, EmmanuelPrando, CarolinaGiliani, SilviaIsraelsson, ElisabethXu, ZhaohuiAbhyankar, AvinashIsraël, LauraTrevejo-Nunez, GiraldinaBogunovic, DusanCepika, Alma-MartinaMacDuff, DonnaChrabieh, MayaHubeau, MarjorieBajolle, FannyDebré, MarianneMazzolari, EvelinaVairo, DonatellaAgou, FabriceVirgin, Herbert W.Bossuyt, XavierRambaud, CarolineFacchetti, FabioBonnet, DamienQuartier, PierreFournet, Jean-ChristophePascual, VirginiaChaussabel, DamienNotarangelo, LuigiPuel, AnneIsraël, AlainCasanova, Jean-LaurentPicard, Capucine2014-02-132012Boisson, B., E. Laplantine, C. Prando, S. Giliani, E. Israelsson, Z. Xu, A. Abhyankar, et al. 2012. “Immunodeficiency, auto-inflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency.” Nature immunology 13 (12): 1178-1186. doi:10.1038/ni.2457. http://dx.doi.org/10.1038/ni.2457.1529-2908http://nrs.harvard.edu/urn-3:HUL.InstRepos:11708667We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic auto-inflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1, a component the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin-1β (IL-1β) was compromised in the patients’ fibroblasts. By contrast, the patients’ mononuclear leukocytes, particularly monocytes, were hyperresponsive to IL-1β. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1β responses thus differed between cell types, consistent with the unique association of auto-inflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1β responses differently in different cell types.en-USJournal Article2014-02-1310.1038/ni.2457