ArticleThe Journal of experimental medicine2020
Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome.
Erratum issued Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 78 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 2 pooled it
6.1field-weighted citation impact, top 3% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Genome-Scale Meta-analysis of Host Responses to Staphylococcus aureus Identifies Pathways for Host-Directed Therapeutic Targeting.The Journal of infectious diseases · 2025Pooled it
- French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes.Orphanet journal of rare diseases · 2023Guideline
- Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling.Frontiers in immunology · 2022Trial
- Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome.The Journal of clinical investigation · 2020Trial
- Autosomal recessive OSMRβ deficiency: Connecting OSM and/or IL-31 with atopy.Journal of human immunity · 2026Article
- Clinical features, genetics, treatment, and long-term outcomes of STAT3 hyper-IgE syndrome: Single-center cohort analysis.The Journal of allergy and clinical immunology · 2026Observational
- Human germline biallelic loss-of-functionJournal of human immunity · 2026Article
- Oncostatin M receptor deficiency as a novel candidate genetic cause of autosomal recessive hyper-IgE syndrome.Journal of human immunity · 2026Article
- Mixed Signals: T Cells as Architects of IgE Immunity.Immunological reviews · 2026Review
- ERK1/2 hijack STAT3 via Thr714 phosphorylation to suppress gene expression.Cell communication and signaling : CCS · 2026Article
- Non-canonical IL‑22 receptor signaling remodels the oral mucosal barrier during Candida albicans immunosurveillance.Nature communications · 2026Article
- Proteolytic profiling of human plasma reveals an immunoactive complement C3 fragment.The EMBO journal · 2025Article
- GATA2 decommissioning of enhancers: A mechanism to constrain inflammatory signaling.Cell reports · 2025Article
- IL6ST participates in the development of adolescent idiopathic scoliosis by regulating bone marrow mesenchymal stem cells.Communications biology · 2025Article
- Fine mapping of heterozygous IL6ST nonsense variants underlying autosomal dominant hyper-IgE syndrome.JCI insight · 2025Article
- Pathological IgE Production in Inborn Errors of Immunity and Beyond.Immunological reviews · 2025Review
- Pulmonary features and stage of disease in adult patients with hyper-IgE syndrome: a single-centre clinical study and literature review.Orphanet journal of rare diseases · 2025Article
- Human immunity to fungal infections.The Journal of experimental medicine · 2025Review
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.The Journal of experimental medicine · 2025Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
60 authors at 18 institutions in 8 countries.
Vivien BéziatLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Simon J TavernierPrimary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
Yin-Huai ChenTranslational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Cindy S MaImmunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
Marie MaternaLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Arian LaurenceTranslational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Jens StaalVIB-UGent Center for Inflammation Research, Unit of Molecular Signal Transduction in Inflammation, Ghent, Belgium.
Dominik AschenbrennerTranslational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Lisa RoelsPrimary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
Lisa WorleyImmunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
Kathleen ClaesCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Lisa GartnerTranslational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Lisa A KohnDivision of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA.
Marieke De BruyneCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Klaus Schmitz-AbeDivision of Newborn Medicine and Neonatal Genomics Program, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Louis-Marie CharbonnierDepartment of Pediatrics, Harvard Medical School, Boston, MA.
Sevgi KelesNecmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey.
Justine NammourLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Natasha VladikineLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Majistor Raj Luxman Maglorius RenkilarajLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Yoann SeeleuthnerLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Mélanie MigaudLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Jérémie RosainLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Mohamed JeljeliCochin University Hospital, Biological Immunology Unit, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France.
Bertrand BoissonLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Eva Van BraeckelDepartment of Respiratory Medicine, Ghent University Hospital, Ghent Belgium.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Hongzheng DaiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Lindsay C BurrageDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
David R MurdockDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Bart N LambrechtVIB-UGent Center for Inflammation Research, Unit of Immunoregulation and Mucosal Immunology, Ghent, Belgium.
Véronique Avettand-FenoelLaboratory of Clinical Microbiology, Virology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France.
Tiphanie P VogelDivision of Rheumatology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX.
Undiagnosed Diseases Network
Charles R EstherPediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Sule HaskologluDivision of Pediatric Immunology and Allergy, Ankara University School of Medicine, Sıhhıye, Ankara, Turkey.
Figen DoguDivision of Pediatric Immunology and Allergy, Ankara University School of Medicine, Sıhhıye, Ankara, Turkey.
Peter CiznarDepartment of Pediatrics, Faculty of Medicine Comenius University and Children's University Hospital, Bratislava, Slovakia.
David BoutboulClinical Immunology Department, Saint Louis Hospital, AP-HP de Paris University of Paris, Paris, France.
Marie Ouachée-ChardinDepartment of Pediatric Hematology and Immunology, Robert Debré Hospital, AP-HP, Paris, France.
Jean AmourettePulmonology Department, Centre Hospitalier d'Arras, Arras, France.
Marie-Noëlle LebrasPediatric Pulmonology, Infectious Disease and Internal Medicine Department, AP-HP, Robert Debré Hospital, Paris, France.
Clément GauvainThoracic Oncology Department, Lille University Hospital, Lille, France.
Colas TcherakianHôpital Foch, Pulmonology Department, Suresnes, France.
Aydan IkinciogullariDivision of Pediatric Immunology and Allergy, Ankara University School of Medicine, Sıhhıye, Ankara, Turkey.
Rudi BeyaertVIB-UGent Center for Inflammation Research, Unit of Molecular Signal Transduction in Inflammation, Ghent, Belgium.
Laurent AbelLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Joshua D MilnerNational Institute of Allergy and Infectious Diseases, Bethesda, MD.
Bodo GrimbacherInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany.
Louis-Jean CoudercHôpital Foch, Pulmonology Department, Suresnes, France.
Manish J ButteDivision of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA.
Alexandra F FreemanNational Institute of Allergy and Infectious Diseases, Bethesda, MD.
Émilie CatherinotHôpital Foch, Pulmonology Department, Suresnes, France.
Claire FieschiClinical Immunology Department, Saint Louis Hospital, AP-HP de Paris University of Paris, Paris, France.
Talal A ChatilaDepartment of Pediatrics, Harvard Medical School, Boston, MA.
Stuart G TangyeImmunology Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
Holm H UhligTranslational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Filomeen HaerynckPrimary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
Jean-Laurent CasanovaLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Anne PuelLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.
Inserm · FRGhent University Hospital · BEBaylor College of Medicine · USAnkara University · TRBoston Children's Hospital · USJohn Radcliffe Hospital · GBAssistance Publique – Hôpitaux de Paris · FRGarvan Institute of Medical Research · AUUniversity of California, Los Angeles · USHoward Hughes Medical Institute · USUniversité de Lille · FRUniversité Paris Cité · FRUniversity of Freiburg · DEUniversity of North Carolina at Chapel Hill · USHôpital Cochin · FRNational Institute of Allergy and Infectious Diseases · USNecmettin Erbakan University · TRVIB-UGent Center for Inflammation Research · BE
Funding
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MRegulation of IgA class switching in the intestinal mucosaP01AI061093 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI CUNNINGHAM-RUNDLES, CHARLOTTE · 2004 to 2021
$29.8MYale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8MPilot of New Technologies to Increase the Genomic Diagnosis of Undiagnosed Disease Network (UDN) PatientsU01HG007709 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI BACINO, CARLOS A., LEE, BRENDAN · 2014 to 2022
$14.3MNHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9MGenome-wide search for inborn errors of IL-17 immunity underlying chronic mucocutaneous candidiasisR01AI127564 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Jean-Laurent Casanova · 2017 to 2026
$4.8MMechanisms of Disease Pathogenesis in Regulatory T cell DeficiencyR01AI085090 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHATILA, TALAL AMINE, WILLIAMS, CALVIN B · 2010 to 2020
$3.9MMechanisms of Combined Immunodeficiency due to DOCK8 DeficiencyR01AI128976 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI CHATILA, TALAL AMINE · 2018 to 2021
$1.4MHoward Hughes Medical InstituteNCATS NIH HHS UL1 TR001866NHGRI NIH HHS U01 HG007709NHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006504NIAID NIH HHS P01 AI061093NIAID NIH HHS R01 AI085090NIAID NIH HHS R01 AI127564NIAID NIH HHS R01 AI128976
Abstract
Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients' heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways.
Indexed as
Genes, DominantAdolescentAllelesCell MembraneCells, CulturedChildC-Reactive ProteinCytokine Receptor gp130CytokinesFemaleFibroblastsGenetics, PopulationHEK293 CellsHumansJob SyndromeKineticsC-Reactive ProteinCytokine Receptor gp130CytokinesIL6ST protein, human
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Read underepoch 390
Registered trials
NCT02450851ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.