1. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency
- Author
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Maya Chrabieh, Herbert W. Virgin, Evelina Mazzolari, Laura Israel, Alain Israël, Damien Chaussabel, Anne Puel, Jean-Laurent Casanova, Pierre Quartier, Donna A. MacDuff, Avinash Abhyankar, Elisabeth Israelsson, Marianne Debré, Capucine Picard, Fabrice Agou, Fanny Bajolle, Virginia Pascual, Dusan Bogunovic, Marjorie Hubeau, Giraldina Trevejo-Nunez, Carolina Prando, Fabio Facchetti, Silvia Giliani, Bertrand Boisson, Alma-Martina Cepika, Xavier Bossuyt, Damien Bonnet, Jean-Christophe Fournet, Emmanuel Laplantine, Luigi D. Notarangelo, Donatella Vairo, Caroline Rambaud, Zhaohui Xu, Rockefeller University [New York], Signalisation Moléculaire et Activation Cellulaire (SMAC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Brescia [Brescia], Benaroya Research Institute [Seattle] (BRI), Baylor Institute for Immunology Research (BIIR), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biochimie Structurale et Cellulaire, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Hôpital Raymond Poincaré [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Harvard Medical School [Boston] (HMS), This work was partly funded by US National Center for Advancing Translational Sciences and National Center for Research Resources, US National Institutes of Health (NIH, 8UL1TR000043), St. Giles Foundation, Jeffrey Modell Foundation, Rockefeller University, INSERM, Paris Descartes University, US National Institute of Allergy and Infectious Diseases (R21AI085523, J.-L.C. and D.C.), NIH (5P01AI061093, J.-L.C.), NIH (R01AR050770, V.P.), Canceropole Ile de France (2007, A.I.), European Community Network of Excellence-Role of Ubiquitin and Ubiquitin-like Modifiers in Cellular Regulation (LSHC-CT-2005-018683, E.L. and A.I.), Thrasher Research Fund (C. Prando), Institut de Recherches Servier (E.L., F.A. and A.I.) and Manton Foundation (L.D.N.)., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Brescia = University of Brescia (UniBs)
- Subjects
[SDV]Life Sciences [q-bio] ,Interleukin-1beta ,MESH: NF-kappa B ,Cell Cycle Proteins ,MESH: Monocytes ,Monocytes ,0302 clinical medicine ,MESH: Glycogen Storage Disease Type IV ,Ubiquitin ,MESH: Interleukin-1beta ,Immunology and Allergy ,Glycogen storage disease type IV ,Immunodeficiency ,Oligonucleotide Array Sequence Analysis ,0303 health sciences ,biology ,NF-kappa B ,Bacterial Infections ,MESH: Transcription Factors ,3. Good health ,Interleukin 1β ,MESH: Repressor Proteins ,Cell type ,MESH: Immunologic Deficiency Syndromes ,MESH: Bacterial Infections ,Ubiquitin-Protein Ligases ,Immunology ,Protein Serine-Threonine Kinases ,Article ,MESH: Protein-Serine-Threonine Kinases ,Cell Line ,03 medical and health sciences ,Glycogen Storage Disease Type IV ,MESH: Cell Cycle Proteins ,medicine ,Humans ,Transcription factor ,030304 developmental biology ,MESH: Humans ,Hereditary Autoinflammatory Diseases ,Immunologic Deficiency Syndromes ,Ubiquitination ,Fibroblasts ,NFKB1 ,medicine.disease ,MESH: Ubiquitin-Protein Ligases ,MESH: Cell Line ,Repressor Proteins ,Cell culture ,MESH: Fibroblasts ,MESH: Oligonucleotide Array Sequence Analysis ,biology.protein ,MESH: Ubiquitination ,MESH: Hereditary Autoinflammatory Diseases ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
International audience; 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.
- Published
- 2012