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Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency.
Oda, Hirotsugu; Manthiram, Kalpana; Chavan, Pallavi Pimpale; Rieser, Eva; Veli, Önay; Kaya, Öykü; Rauch, Charles; Nakabo, Shuichiro; Kuehn, Hye Sun; Swart, Mariël; Wang, Yanli; Çelik, Nisa Ilgim; Molitor, Anne; Ziaee, Vahid; Movahedi, Nasim; Shahrooei, Mohammad; Parvaneh, Nima; Alipour-Olyei, Nasrin; Carapito, Raphael; Xu, Qin; Preite, Silvia; Beck, David B; Chae, Jae Jin; Nehrebecky, Michele; Ombrello, Amanda K; Hoffmann, Patrycja; Romeo, Tina; Deuitch, Natalie T; Matthíasardóttir, Brynja; Mullikin, James; Komarow, Hirsh; Stoddard, Jennifer; Niemela, Julie; Dobbs, Kerry; Sweeney, Colin L; Anderton, Holly; Lawlor, Kate E; Yoshitomi, Hiroyuki; Yang, Dan; Boehm, Manfred; Davis, Jeremy; Mudd, Pamela; Randazzo, Davide; Tsai, Wanxia Li; Gadina, Massimo; Kaplan, Mariana J; Toguchida, Junya; Mayer, Christian T; Rosenzweig, Sergio D; Notarangelo, Luigi D.
Afiliación
  • Oda H; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. hoda@uni-koeln.de.
  • Manthiram K; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. hoda@uni-koeln.de.
  • Chavan PP; Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. hoda@uni-koeln.de.
  • Rieser E; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Veli Ö; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kaya Ö; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Rauch C; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Nakabo S; Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
  • Kuehn HS; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Swart M; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Wang Y; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Çelik NI; Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
  • Molitor A; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ziaee V; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Movahedi N; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Shahrooei M; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Parvaneh N; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Alipour-Olyei N; Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d'Immunologie et d'Hématologie, CRBS, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg,
  • Carapito R; Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France.
  • Xu Q; Division of Rheumatology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.
  • Preite S; Children's Medical Center, Pediatrics Center of Excellence, Tehran, Iran.
  • Beck DB; Pediatric Rheumatology Society of Iran, Tehran, Iran.
  • Chae JJ; Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran, Iran.
  • Nehrebecky M; Children's Medical Center, Pediatrics Center of Excellence, Tehran, Iran.
  • Ombrello AK; Pediatric Rheumatology Society of Iran, Tehran, Iran.
  • Hoffmann P; School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
  • Romeo T; Clinical and Diagnostic Immunology, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.
  • Deuitch NT; Dr. Shahrooei Lab, 22 Bahman St., Ashrafi Esfahani Blvd, Tehran, Iran.
  • Matthíasardóttir B; Children's Medical Center, Pediatrics Center of Excellence, Tehran, Iran.
  • Mullikin J; Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.
  • Komarow H; Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d'Immunologie et d'Hématologie, CRBS, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg,
  • Stoddard J; Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France.
  • Niemela J; Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d'Immunologie et d'Hématologie, CRBS, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg,
  • Dobbs K; Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France.
  • Sweeney CL; Laboratoire d'Immunologie, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France.
  • Anderton H; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Lawlor KE; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Yoshitomi H; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Yang D; Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY, USA.
  • Boehm M; Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
  • Davis J; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Mudd P; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Randazzo D; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Tsai WL; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Gadina M; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Kaplan MJ; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Toguchida J; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Mayer CT; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Rosenzweig SD; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Notarangelo LD; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Nat Immunol ; 25(5): 764-777, 2024 May.
Article en En | MEDLINE | ID: mdl-38609546
ABSTRACT
The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficiency, autoinflammation and glycogen storage disease. In mice, the loss of Sharpin leads to severe dermatitis due to excessive keratinocyte cell death. Here, we report two individuals with SHARPIN deficiency who manifest autoinflammatory symptoms but unexpectedly no dermatological problems. Fibroblasts and B cells from these individuals showed attenuated canonical NF-κB responses and a propensity for cell death mediated by TNF superfamily members. Both SHARPIN-deficient and HOIP-deficient individuals showed a substantial reduction of secondary lymphoid germinal center B cell development. Treatment of one SHARPIN-deficient individual with anti-TNF therapies led to complete clinical and transcriptomic resolution of autoinflammation. These findings underscore the critical function of the LUBAC as a gatekeeper for cell death-mediated immune dysregulation in humans.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Ubiquitinas / Síndromes de Inmunodeficiencia / Proteínas del Tejido Nervioso Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Ubiquitinas / Síndromes de Inmunodeficiencia / Proteínas del Tejido Nervioso Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos