ArticleNature immunology2024
Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency.
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Article in Nature immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress.Cell death and differentiation · 2026Article
- Pyoderma gangrenosum caused by the molecular uncoupling of OTULIN catalytic activity and LUBAC binding.Nature immunology · 2026Article
- The E3 Ligase RNF115 Aggravates Pathological Cardiac Hypertrophy via Ubiquitin-Mediated Degradation of SPTBN1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Necroptosis triggers inflammatory interferon signatures in patient-derived metastatic breast cancer organoids.Signal transduction and targeted therapy · 2026Article
- The atypical E3 ligase HOIL-1 safeguards the ribosome during cellular stress.Nature cell biology · 2026Article
- CD8Nature communications · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- TAB2 controls a TAK1-independent cell death checkpoint at the level of TNFR1 complex II in the TNF pathway.Cell death and differentiation · 2026Article
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Article
- Dual-omics analysis of key biomarkers in T cell ubiquitination of rheumatoid arthritis blood and synovial tissue, validated by two-sample Mendelian randomization and qPCR.Frontiers in immunology · 2026Article
- Association of peripheral blood LUBAC and OTULIN expression with severity and outcome in acute ischemic stroke: a prospective cohort study.Frontiers in immunology · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Human inborn errors of type I interferon-independent intrinsic immunity in nonleukocytic cells.Current opinion in immunology · 2025Review
- Novel genotypes, phenotypes, and triggers in humans with OTULIN haploinsufficiency.Journal of human immunity · 2025Article
- Update on new autoinflammatory disorders from the 2024 Pediatric Rheumatology European Society Congress.Pediatric rheumatology online journal · 2025Review
- Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome.Science advances · 2025Article
- Insights from the 2024 pediatric rheumatology basic/translational years in review.Pediatric rheumatology online journal · 2025Review
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee.Journal of human immunity · 2025Article
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Authors and funding
62 authors at 13 institutions in 9 countries.
Hirotsugu Oda *National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. hoda@uni-koeln.de.ORCID http://orcid.org/0000-0002-1411-5381
Kalpana Manthiram *National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-6451-8173
Pallavi Pimpale ChavanNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5124-6559
Eva RieserCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Önay VeliCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Öykü KayaCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Charles RauchCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Shuichiro NakaboNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9250-1851
Hye Sun KuehnDepartment of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Mariël SwartCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.ORCID http://orcid.org/0009-0007-8969-8976
Yanli WangCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Nisa Ilgim ÇelikCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.ORCID http://orcid.org/0009-0008-4864-0038
Anne MolitorLaboratoire 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, France.
Vahid ZiaeeDivision of Rheumatology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.ORCID http://orcid.org/0000-0003-4648-3573
Nasim MovahediChildren's Medical Center, Pediatrics Center of Excellence, Tehran, Iran.ORCID http://orcid.org/0000-0003-2492-688X
Mohammad ShahrooeiClinical and Diagnostic Immunology, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.
Nima ParvanehChildren's Medical Center, Pediatrics Center of Excellence, Tehran, Iran.
Nasrin Alipour-OlyeiLaboratoire 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, France.
Raphael CarapitoLaboratoire 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, France.ORCID http://orcid.org/0000-0002-7036-442X
Qin XuNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1812-3108
Silvia PreiteNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
David B BeckNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5884-6231
Jae Jin ChaeNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Michele NehrebeckyNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Amanda K OmbrelloNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Patrycja HoffmannNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Tina RomeoNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Natalie T DeuitchNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0146-1162
Brynja MatthíasardóttirNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
James MullikinNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0825-3750
Hirsh KomarowNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jennifer StoddardDepartment of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Julie NiemelaDepartment of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Kerry DobbsNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3432-3137
Colin L SweeneyNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Holly AndertonThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0003-3913-9686
Kate E LawlorThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0003-0471-6842
Hiroyuki YoshitomiInstitute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0001-7339-9030
Dan YangNational Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Manfred BoehmNational Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Jeremy DavisNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Pamela MuddDivision of Pediatric Otolaryngology, Children's National Hospital, Washington, DC, USA.
Davide RandazzoNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Wanxia Li TsaiNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Massimo GadinaNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Mariana J KaplanNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2968-0815
Junya ToguchidaInstitute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Christian T MayerNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0256-9650
Sergio D RosenzweigDepartment of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Luigi D NotarangeloNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8335-0262
Kazuhiro IwaiGraduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0001-5620-5951
John SilkeThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0002-7611-5774
Pamela L SchwartzbergNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Bertrand BoissonSt. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0001-5240-3555
Jean-Laurent CasanovaSt. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0002-7782-4169
Seiamak BahramLaboratoire 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, France.ORCID http://orcid.org/0000-0002-6928-9952
Anand Prahalad RaoManipal Hospital, Bengaluru, India.
Nieves PeltzerCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0002-4134-5852
Henning WalczakCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Najoua LalaouiThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. najoua.lalaoui@petermac.org.ORCID http://orcid.org/0000-0002-0165-3324
Ivona AksentijevichNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. aksentii@mail.nih.gov.ORCID http://orcid.org/0000-0002-6564-7214
Daniel L KastnerNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. dan.kastner@nih.gov.ORCID http://orcid.org/0000-0001-7188-4550
National Institutes of Health · USUniversity of Cologne · DEInserm · FRNational Institutes of Health Clinical Center · USKyoto University · JPThe University of Melbourne · AUChildren's Medical Center · IRChildren's National · USGolestan University · IRHoward Hughes Medical Institute · USKU Leuven · BEManipal Hospital · INWalter and Eliza Hall Institute of Medical Research · AU
Funding
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MSystemic AutoimmunityZIAAR041199 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI KAPLAN, MARIANA · 2014 to 2025
$32.5MRegulation of IgA class switching in the intestinal mucosaP01AI061093 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI CUNNINGHAM-RUNDLES, CHARLOTTE · 2004 to 2021
$29.8MGenetics, Pathophysiology, and Treatment of Recessive Autoinflammatory DiseasesZIAHG200372 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI KASTNER, DANIEL · 2011 to 2025
$27.2MVascular remodeling in patients with rare genetic disordersZIAHL006077 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BOEHM, MANFRED · 2010 to 2025
$22.9MGenetic and Biochemical Approaches to Tyrosine Kinase and Lymphocyte SignalingZIAAI001240 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SCHWARTZBERG, PAMELA · 2019 to 2025
$18.8MNIAMS Light Imaging FacilityZICAR041186 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI RANDAZZO, DAVIDE · 2010 to 2025
$18.2MCharacterization of the cellular and molecular bases of inborn errors of immunityZIAAI001222 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2017 to 2025
$15.2MThe role of apoptosis in B lymphocyte biologyZIABC011975 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MAYER, CHRISTIAN · 2020 to 2025
$5.2MImmunology of Pediatric Tonsil DisordersZIAAI001340 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MANTHIRAM, KALPANA · 2021 to 2025
$1.9MAutosomal dominant OTULIN deficiency and staphylococcal diseaseR21AI159728 · NIAID · ROCKEFELLER UNIVERSITY · PI BOISSON, BERTRAND, SPAAN, ANDRAS NIKO · 2022 to 2023
$466kAgence Nationale de la Recherche (French National Research Agency) ANR-10-IDEX-0002Agence Nationale de la Recherche (French National Research Agency) ANR-11-LABX-0070_TRANSPLANTEXAgence Nationale de la Recherche (French National Research Agency) ANR-20-SFRI-0012Cancer Research UK (CRUK) A27323Department of Health | National Health and Medical Research Council (NHMRC) 1194144Department of Health | National Health and Medical Research Council (NHMRC) 1195038Department of Health | National Health and Medical Research Council (NHMRC) 2017929Department of Health | National Health and Medical Research Council (NHMRC) GNT9000719Deutsche Forschungsgemeinschaft (German Research Foundation) 390661388Deutsche Forschungsgemeinschaft (German Research Foundation) 413326622Deutsche Forschungsgemeinschaft (German Research Foundation) 414786233Deutsche Forschungsgemeinschaft (German Research Foundation) 455784452Fritz Thyssen Stiftung (Fritz Thyssen Foundation) 10.23.1.013MNNCATS NIH HHS UL1 TR001866NIAID NIH HHS P01 AI061093NIAID NIH HHS R21 AI159728RCUK | Medical Research Council (MRC) MR/S00811X/1Wellcome Trust 214342Wellcome Trust (Wellcome) 214342/Z/18/Z
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.
Indexed as
Immunologic Deficiency SyndromesNerve Tissue ProteinsUbiquitinsAllelesAnimalsB-LymphocytesFemaleFibroblastsHumansInflammationIntracellular Signaling Peptides and ProteinsLoss of Function MutationMaleMiceNF-kappa BUbiquitin-Protein LigasesIntracellular Signaling Peptides and ProteinsNerve Tissue ProteinsNF-kappa BsharpinSHARPIN protein, humanUbiquitin-Protein LigasesUbiquitins
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