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

Bertrand Boisson 1 Emmanuel Laplantine 2 Carolina Prando 1 Silvia Giliani 3 Elisabeth Israelsson 4 Zhaohui Xu 5 Avinash Abhyankar 1 Laura Israël 6 Giraldina Trevejo-Nunez 1 Dusan Bogunovic 1 Alma-Martina Cepika 5 Donna Macduff 7 Maya Chrabieh 6 Marjorie Hubeau 6 Fanny Bajolle 8 Marianne Debré 8 Evelina Mazzolari 3 Donatella Vairo 3 Fabrice Agou 9 Herbert Virgin 7 Xavier Bossuyt 10 Caroline Rambaud 11 Fabio Facchetti 3 Damien Bonnet 12, 8 Pierre Quartier 12, 8 Jean-Christophe Fournet 12, 8 Virginia Pascual 5 Damien Chaussabel 4, 5 Luigi Notarangelo 13 Anne Puel 6 Alain Israël 2 Jean-Laurent Casanova 1, 6, 8, * Capucine Picard 6, 8
* Corresponding author
1 Rockefeller University [New York]
2 SMAC - Signalisation Moléculaire et Activation Cellulaire
3 Università degli Studi di Brescia [Brescia]
4 BRI - Benaroya Research Institute [Seattle]
5 BIIR - Baylor Institute for Immunology Research
6 Inserm U980 - Génétique Humaine des Maladies Infectieuses
7 Washington University School of Medicine in St. Louis
8 CHU Necker - Enfants Malades [AP-HP]
9 Biochimie Structurale et Cellulaire
10 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
11 Hôpital Raymond Poincaré [AP-HP]
12 UPD5 - Université Paris Descartes - Paris 5
13 HMS - Harvard Medical School [Boston]
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-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.
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Submitted on : Friday, July 2, 2021 - 4:23:05 PM
Last modification on : Tuesday, December 7, 2021 - 10:12:30 AM

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PASTEUR | UNIV-PARIS5 | CNRS | UNIV-PARIS

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Bertrand Boisson, Emmanuel Laplantine, Carolina Prando, Silvia Giliani, Elisabeth Israelsson, et al.. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nature Immunology, Nature Publishing Group, 2012, 13 (12), pp.1178-1186. ⟨10.1038/ni.2457⟩. ⟨pasteur-03277102⟩

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