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- Title
Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency.
- Authors
Boisson, Bertrand; Laplantine, Emmanuel; Prando, Carolina; Giliani, Silvia; Israelsson, Elisabeth; Xu, Zhaohui; Abhyankar, Avinash; Israël, Laura; Trevejo-Nunez, Giraldina; Bogunovic, Dusan; Cepika, Alma-Martina; MacDuff, Donna; Chrabieh, Maya; Hubeau, Marjorie; Bajolle, Fanny; Debré, Marianne; Mazzolari, Evelina; Vairo, Donatella; Agou, Fabrice; Virgin, Herbert W
- Abstract
We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic autoinflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1), a component of the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-?B activation in response to interleukin 1? (IL-1?) was compromised in the patients' fibroblasts. By contrast, the patients' mononuclear leukocytes, particularly monocytes, were hyper-responsive to IL-1?. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1? responses thus differed between cell types, consistent with the unique association of autoinflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-?B-dependent IL-1? responses differently in different cell types.
- Subjects
BACTERIAL diseases; IMMUNODEFICIENCY; INFLAMMATION; GENE expression; GENETIC mutation; NF-kappa B; CELL differentiation
- Publication
Nature Immunology, 2012, Vol 13, Issue 12, p1178
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2457