ArticleThe Journal of experimental medicine2015
Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome.
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Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers, 3 of them syntheses that pooled it.
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219citing papers in PubMed, 3 pooled it
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Who cites it
219 citing papers in PubMed, 3 syntheses or guidelines pooled it, 352 citations in OpenAlex.
- Association of germline TYK2 variation with lung cancer and non-Hodgkin lymphoma risk.International journal of cancer · 2022Pooled it
- An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China.Frontiers in immunology · 2022Pooled it
- Successful Hematopoietic Stem Cell Transplantation in a Patient with Complete IFN-γ Receptor 2 Deficiency: a Case Report and Literature Review.Journal of clinical immunology · 2020Pooled it
- Trial
- The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses.The Journal of experimental medicine · 2018Trial
- Prevalence of neutralizing autoantibodies against type I interferon in dengue patients.Journal of human immunity · 2026Article
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- Genetic variations on influenza virus infection outcomes in Moroccan patients.Iranian journal of microbiology · 2026Article
- TYK2 mediates neuroinflammation in Alzheimer's disease brains with TDP-43 pathology.Nature communications · 2026Article
- Monogenic disorders of immunity: Common variants are not so rare.Cell genomics · 2026Review
- Mendelian susceptibility to mycobacterial disease: IFN-γ-driven immunity collapse underlies heterogeneous infections.Frontiers in immunology · 2026Review
- Mechanisms of Differential Signal Transduction by Interferon Lambda Receptor 1 Variants.Journal of innate immunity · 2026Article
- Article
- Tyrosine kinase 2 inhibitors in the therapy of inflammatory and autoimmune diseases.Pharmacological reports : PR · 2025Review
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- Atopic dermatitis in inborn errors of immunity: at the interface of immunodeficiency and immune dysregulation.Immunologic research · 2025Review
- Mechanisms of Differential Signal Transduction by IFNLR1 Variants.bioRxiv : the preprint server for biology · 2025Article
- The potential impacts of human genetics on virus emergence.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mepolizumab treatment in a child with inherited TYK2 deficiency.Journal of human immunity · 2025Article
- Interferons in health and disease.Cell · 2025Review
159 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
54 authors at 20 institutions in 15 countries.
Alexandra Y KreinsSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 Weill Cornell Graduate School of Medical Sciences, New York, NY 10065.
Michael J CiancanelliSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Satoshi OkadaSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Xiao-Fei KongSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Noé Ramírez-AlejoSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Sara Sebnem KilicDepartment of Pediatric Immunology, Uludağ University Faculty of Medicine, 16059 Görükle, Bursa, Turkey.
Jamila El BaghdadiGenetics Unit, Military Hospital Mohamed V, Hay Riad, 10100 Rabat, Morocco.
Shigeaki NonoyamaDepartment of Pediatrics, National Defense Medical College, Tokorozawa, Saitama 359-0042, Japan.
Seyed Alireza MahdavianiPediatric Respiratory Diseases Research Center; and Department of Clinical Immunology and Infectious Diseases, Masih Daneshvari Hospital; National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, 141556153 Tehran, Iran.
Fatima AilalClinical Immunology Unit, Department of Pediatrics, King Hassan II University, CHU Ibn Rochd, 20000 Casablanca, Morocco.
Aziz BousfihaClinical Immunology Unit, Department of Pediatrics, King Hassan II University, CHU Ibn Rochd, 20000 Casablanca, Morocco.
Davood MansouriPediatric Respiratory Diseases Research Center; and Department of Clinical Immunology and Infectious Diseases, Masih Daneshvari Hospital; National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, 141556153 Tehran, Iran.
Elma NievasImmunology Unit, Pediatric Hospital A. Fleming-OSEP, Mendoza 5500, Argentina.
Cindy S MaImmunology Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia St. Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
Geetha RaoImmunology Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Andrea BernasconiImmunology and Rheumatology Service, Garrahan Hospital, Buenos Aires 1408, Argentina.
Hye Sun KuehnDepartment of Laboratory Medicine, Clinical Center; and Primary Immunodeficiency Clinic, National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, MD 20892.
Julie NiemelaDepartment of Laboratory Medicine, Clinical Center; and Primary Immunodeficiency Clinic, National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, MD 20892.
Jennifer StoddardDepartment of Laboratory Medicine, Clinical Center; and Primary Immunodeficiency Clinic, National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, MD 20892.
Paul DeveauLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France.
Aurelie CobatLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France.
Safa El AzbaouiGenetics Unit, Military Hospital Mohamed V, Hay Riad, 10100 Rabat, Morocco Faculty of Science-Kenitra, Ibn Tofaïl University, 14000 Kenitra, Morocco.
Ayoub SabriGenetics Unit, Military Hospital Mohamed V, Hay Riad, 10100 Rabat, Morocco Faculty of Science-Kenitra, Ibn Tofaïl University, 14000 Kenitra, Morocco.
Che Kang LimDivision of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden Department of Clinical Research, Singapore General Hospital, Singapore 169856.
Mikael SundinPediatric Hematology/Immunology, Astrid Lindgrens Children's Hospital and Karolinska Institutet, 141 86 Stockholm, Sweden.
Danielle T AveryImmunology Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Rabih HalwaniAsthma Research Chair and Prince Naif Center for Immunology Research, Department of Pediatrics, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia.
Audrey V GrantLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France.
Bertrand BoissonSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Dusan BogunovicSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Yuval ItanSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Marcela Moncada-VelezSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 Group of Primary Immunodeficiencies, Institute of Biology, University of Antioquia UdeA, 1226 Medellín, Colombia.
Ruben Martinez-BarricarteSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Melanie MigaudLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France.
Caroline DeswarteLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France.
Laia AlsinaBaylor Institute for Immunology Research and Baylor Research Institute, Dallas, TX 75204 Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, TX 75204 Allergy and Clinical Immunology Department, Hospital Sant Joan de Deu, Barcelona University, 08950 Barcelona, Spain.
Daniel KotlarzDepartment of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, D-80337 Munich, Germany.
Christoph KleinDepartment of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, D-80337 Munich, Germany.
Ingrid Muller-FleckensteinInstitute of Clinical and Molecular Virology, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany.
Bernhard FleckensteinInstitute of Clinical and Molecular Virology, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany.
Valerie Cormier-DaireDepartment of Genetics, INSERM U1163, University Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Necker Enfants Malades Hospital, 75015 Paris, France.
Stefan Rose-JohnInstitute of Biochemistry, University of Kiel, D-24098 Kiel, Germany.
Capucine PicardSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Enfants Malades Hospital, 75015 Paris, France.
Lennart HammarstromDivision of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 52 Stockholm, Sweden.
Anne PuelLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France.
Saleh Al-MuhsenAsthma Research Chair and Prince Naif Center for Immunology Research, Department of Pediatrics, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia.
Laurent AbelSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France.
Damien ChaussabelSystems Biology Department, Sidra Medical and Research Center, Doha, Qatar.
Sergio D RosenzweigDepartment of Laboratory Medicine, Clinical Center; and Primary Immunodeficiency Clinic, National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, MD 20892 Department of Laboratory Medicine, Clinical Center; and Primary Immunodeficiency Clinic, National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, MD 20892.
Yoshiyuki MinegishiDepartment of Immune Regulation, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
Stuart G TangyeImmunology Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia St. Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
Jacinta BustamanteLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Enfants Malades Hospital, 75015 Paris, France.
Jean-Laurent CasanovaSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France Pediatric Immunology and Hematology Unit, Necker Enfants Malades Hospital, 75015 Paris, France Howard Hughes Medical Institute, New York, NY 10065.
Stéphanie Boisson-DupuisSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Enfants Malades Hospital, 75015 Paris, France University Paris Descartes, Imagine Institute, 75006 Paris, France stbo603@rockefeller.edu.
Rockefeller University · USInserm · FRInstitut des Maladies Génétiques Imagine · FRNational Institute of Allergy and Infectious Diseases · USFriedrich-Alexander-Universität Erlangen-Nürnberg · DEGarvan Institute of Medical Research · AUKing Saud University · SALudwig-Maximilians-Universität München · DEUniversité Ibn-Tofail · MAUniversity of Hassan II Casablanca · MABaylor University · USBursa Uludağ Üni̇versi̇tesi̇ · TRGarrahan Hospital · ARHôpital Militaire Moulay Ismail · MAHoward Hughes Medical Institute · USKarolinska Institutet · SEKarolinska University Hospital · SEKiel University · DEMasih Daneshvari Hospital · IRNational Defense Medical College · JP
Funding
Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8MGenome-Wide Dissection of Mendelian Susceptibility to Mycobacterial DiseaseR37AI095983 · NIAID · ROCKEFELLER UNIVERSITY · PI CASANOVA, JEAN-LAURENT · 2011 to 2020
$4.6MGenetic predisposition to tuberculosis in MoroccoU01AI088685 · NIAID · ROCKEFELLER UNIVERSITY · PI ABEL, LAURENT, CASANOVA, JEAN-LAURENT · 2010 to 2014
$3.3MA genetic dissection of Mendelian susceptibility to mycobacterial diseases (MSMD)R01AI089970 · NIAID · ROCKEFELLER UNIVERSITY · PI CASANOVA, JEAN-LAURENT · 2010 to 2014
$2.5MISG15 responsive pathwayK99AI106942 · NIAID · ROCKEFELLER UNIVERSITY · PI BOGUNOVIC, DUSAN · 2013 to 2013
$106kMutation Analysis Of Selected Lymphoid Immune DisordersZIACL010304 · CLC · CLINICAL CENTER · PI ROSENZWEIG, SERGIO · 2009 to 2025
$0kEuropean Research Council 268777NCATS NIH HHS 8UL1TR000043NCATS NIH HHS UL1 TR000043NIAID NIH HHS 1K99AI106942NIAID NIH HHS 5R01AI089970NIAID NIH HHS 5R37AI095983NIAID NIH HHS 5U01AI088685NIAID NIH HHS K99 AI106942NIAID NIH HHS R01 AI089970NIAID NIH HHS R37 AI095983NIAID NIH HHS U01 AI088685
Abstract
Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
Indexed as
AdolescentCase-Control StudiesChildChild, PreschoolFemaleHumansInfantInterferon-gammaInterleukin-10Interleukin-12Interleukin-23Interleukin-6Job SyndromeLeukocytesMaleMutationInterferon-gammaInterleukin-10Interleukin-12Interleukin-23Interleukin-6TYK2 KinaseTYK2 protein, human
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