Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency

Bertrand Boisson, Emmanuel Laplantine, Carolina Prando, Silvia Giliani, Elisabeth Israelsson, Zhaohui Xu, Avinash Abhyankar, Laura Israël, Giraldina Trevejo-Nunez, Dusan Bogunovic, Alma Martina Cepika, Donna MacDuff, Maya Chrabieh, Marjorie Hubeau, Fanny Bajolle, Marianne Debré, Evelina Mazzolari, Donatella Vairo, Fabrice Agou, Herbert W. VirginXavier Bossuyt, Caroline Rambaud, Fabio Facchetti, Damien Bonnet, Pierre Quartier, Jean Christophe Fournet, Virginia Pascual, Damien Chaussabel, Luigi D. Notarangelo, Anne Puel, Alain Israël, Jean Laurent Casanova, Capucine Picard

Research output: Contribution to journalArticlepeer-review

293 Scopus citations


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-κB activation in response to interleukin 1β (IL-1β) was compromised in the patients' fibroblasts. By contrast, the patients' mononuclear leukocytes, particularly monocytes, were hyper-responsive 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 autoinflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1β responses differently in different cell types.

Original languageEnglish
Pages (from-to)1178-1186
Number of pages9
JournalNature immunology
Issue number12
StatePublished - Dec 2012


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