ArticleThe Journal of allergy and clinical immunology2023
Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.
Erratum issuedOpen access · greenAbstract read
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Article in The Journal of allergy and clinical immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers, 2 of them syntheses that pooled it.
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71citing papers in PubMed, 2 pooled it
8.7field-weighted citation impact, top 1% of its field
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.
- Pooled it
- Cancer Trends in Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.Journal of clinical immunology · 2024Pooled it
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- Impaired regulation by purinergic signaling axis contributes to CD8+ T cell dysregulation in STAT3 gain of function.JCI insight · 2026Article
- PDLIM4 promotes dephosphorylation of STAT transcription factors by recruiting PTP-BL and inhibits Th1, Th2, and Th17 cell differentiation.International immunology · 2026Article
- Human CD21Journal of human immunity · 2026Review
- Rare variants in genes related to inborn errors of immunity in patients with rheumatoid arthritis and secondary immunodeficiency.RMD open · 2026Article
- From CVID to PIRD: Genetic Testing Leading to Signal Transducer and Activator of Transcription 3 Gain-of-Function Diagnosis and Directed Therapy.The journal of allergy and clinical immunology. In practice · 2026Article
- Ocular manifestations ofAmerican journal of ophthalmology case reports · 2026Article
- Mycobacterium intracellulare Infection in a Japanese Patient with Signal Transducer and Activator of Transcription-3 Gain-of-function Syndrome.Internal medicine (Tokyo, Japan) · 2026Article
- Targeted deep sequencing identifies mosaicism in patients with immune dysregulation.The Journal of allergy and clinical immunology · 2026Article
- The Intertwining Between Arthritis and Inborn Errors of Immunity.Journal of clinical medicine · 2026Review
- Antigen Microarray Reveals Broad and Subclinical Autoimmunity in Patients with Inborn Errors of Immunity.Journal of clinical immunology · 2026Article
- JAK-STAT signaling: molecular mechanism and targeted treatment in dento-maxillofacial abnormalities.International journal of oral science · 2026Review
- Article
- STAT3-Mutated Hyper-IgE Syndrome With Retroperitoneal Abscess in Adolescence.Clinical case reports · 2026Article
- Reduction in mucosal phosphorylated STAT3 under therapy with JAK inhibitor in STAT3 gain of function mutation - a case study.Virchows Archiv : an international journal of pathology · 2026Article
- A case report of ADMIO type 1 caused by aFrontiers in immunology · 2026Article
- ALPS-like Disorder Linked with STAT3 Mutation:Endocrine, metabolic & immune disorders drug targets · 2026Review
- Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.ImmunoTargets and therapy · 2026Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issuedCorrigendum.2024
Authors and funding
110 authors at 20 institutions in 28 countries.
Jennifer W LeidingDivision of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore; Johns Hopkins All Children's Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St Petersburg. Electronic address: jleidin1@jhmi.edu.
Tiphanie P VogelDepartment of Pediatrics, Baylor College of Medicine and William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston.
Valentine G J SantarlasLake Erie College of Osteopathic Medicine, Erie.
Rahul MhaskarDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa.
Madison R SmithDepartment of Pediatrics, Baylor College of Medicine and William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston.
Alexandre CariseyDepartment of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis.
Alexander Vargas-HernándezDepartment of Pediatrics, Baylor College of Medicine and William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston.
Manuel Silva-CarmonaDepartment of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston.
Maximilian HeegInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg.
Anne Rensing-EhlInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg.
Bénédicte NevenLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163-Institut Imagine, Paris.
Jérôme HadjadjLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163-Institut Imagine, Paris.
Sophie HambletonNewcastle University Translational and Clinical Research Institute, Newcastle (United Kingdom).
Timothy Ronan LeahyChildren's Health Ireland at Crumlin, Dublin.
Kornvalee MeesilpavikaiDepartment of Internal Medicine, Division of Clinical Immunology and Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Charlotte Cunningham-RundlesDepartment of Medicine, Mount Sinai School of Medicine, New York.
Cullen M DutmerChildren's Hospital Colorado, University of Colorado School of Medicine, Aurora.
Svetlana O SharapovaBelarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk.
Mervi TaskinenNew Children's Hospital, Pediatric Research Center, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Turku and Kuopio, Finland.
Ignatius ChuaDepartment of Rheumatology, Immunology and Allergy, Christchurch Hospital, Christchurch; Clinical Immunogenomics Research Consortium of Australasia (CIRCA).
Rosie HagueRoyal Hospital for Children, Glasgow.
Christian KlemannDepartment of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover.
Larysa KostyuchenkoCenter of Pediatric Immunology, Western Ukrainian Specialized Children's Medical Centre, Lviv.
Tomohiro MorioDepartment of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo.
Akaluck ThatayatikomDivision of Pediatric Allergy/Immunology/Rheumatology, Shands Children's Hospital, University of Florida, Gainesville.
Ahmet OzenSchool of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul.
Anna ScherbinaDmitry Rogachev National Medical and Research Center for Pediatric Hematology, Oncology and Immunology, Moscow.
Cindy S BauerDivision of Allergy and Immunology, Phoenix Children's Hospital, Phoenix.
Sarah E FlanaganInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter.
Eleonora GambineriDepartment of NEUROFARBA, Section of Children's Health, University of Florence, Anna Meyer Children's Hospital, Florence.
Lisa Giovannini-ChamiPediatric Pulmonology Department, Hôpitaux pédiatriques de Nice CHU-Lenval, Nice.
Jennifer HeimallPerelman School of Medicine at University of Pennsylvania, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia.
Kathleen E SullivanPerelman School of Medicine at University of Pennsylvania, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia.
Eric AllenspachPediatric Immunology/Rheumatology, University of Washington, Seattle; Seattle Children's Hospital, Seattle.
Neil RombergPerelman School of Medicine at University of Pennsylvania, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia.
Sean G DeaneDepartment of Allergy, The Permanente Medical Group, Sacramento, and the Division of Rheumatology/Allergy and Clinical Immunology, University of California, Davis, School of Medicine, Sacramento.
Benjamin T PrinceNationwide Children's Hospital Department of Allergy and Immunology, Columbus; College of Medicine, The Ohio State University, Columbus.
Melissa J RoseCollege of Medicine, The Ohio State University, Columbus; Division of Pediatric Hematology-Oncology, Nationwide Children's Hospital, Columbus.
John BohnsackDepartment of Pediatrics, University of Utah, Salt Lake City.
Talal MousallemDuke Department of Pediatric Allergy and Immunology, Durham.
Rohith JesudasDepartment of Hematology, St Jude Children's Research Hospital, Memphis.
Maria Marluce Dos Santos VilelaPediatric Allergy and Immunology/Center of Investigation in Pediatrics, Faculty of Medical Sciences, State University of Campinas-Unicamp, São Paulo.
Michael O'SullivanClinical Immunogenomics Research Consortium of Australasia (CIRCA); Immunology Department, Perth Children's Hospital, Nedlands.
Jana Pachlopnik SchmidDivision of Immunology, University Children's Hospital Zurich, Children's Research Center (CRC), Zurich.
Štěpánka PrůhováDepartment of Pediatrics, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague.
Adam KlocperkDepartment of Immunology, Second Faculty of Medicine and University Hospital Motol, Charles University in Prague, Prague.
Matthew ReesDepartment of Hematology, St Jude Children's Research Hospital, Memphis.
Helen SuDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
Sami BahnaAllergy and Immunology Section, Louisiana State University Health Sciences Center, Shreveport.
Safa BarisSchool of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul.
Lisa M BartnikasDivision of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston.
Amy Chang BergerDivision of Hospital Medicine, Department of Medicine, University of California, San Francisco.
Tracy A BriggsDivision of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester; NW Genomic Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester.
Shannon BrothersClinical Immunogenomics Research Consortium of Australasia (CIRCA); Starship Children's Hospital, Auckland.
Vanessa BundyAllergy and Immunology, University of California, Los Angeles.
Alice Y ChanDepartment of Medicine, University of California, San Francisco.
Shanmuganathan ChandrakasanDivision of Bone Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta.
Mette ChristiansenDepartment of Clinical Immunology, AUH, Aarhus.
Theresa ColeDepartment of Allergy and Immunology, The Royal Children's Hospital, Melbourne.
Matthew C CookDepartment of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra.
Mukesh M DesaiBai Jerbai Wadia Children Hospital, Mumbai, Parel.
Ute FischerDepartment of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf.
David A FulcherDepartment of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra.
Silvanna GalloDepartment of Pediatrics, Immunology and Rheumatology Section, Puerto Montt Hospital, Puerto Montt.
Amelie GauthierDepartment of Allergy and Immunology, CHU de Québec-CHUL, Laval University Hospital Center, Laval University, Quebec City.
Andrew R GenneryNewcastle University Translational and Clinical Research Institute, Newcastle (United Kingdom).
José Gonçalo MarquesInfectious Diseases and Immunodeficiencies Unit, Department of Pediatrics, Hospital de Santa Maria-CHULN and Faculdade de Medicina, Universidade de Lisboa, Lisbon.
Frédéric GottrandUniversity Lille, Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille.
Bodo GrimbacherInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg.
Eyal GrunebaumDivision of Immunology and Allergy, and the Department of Pediatrics, Developmental and Stem Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto.
Emma HaapaniemiCentre for Molecular Medicine Norway, Oslo; Department of Pediatric Research, Oslo.
Sari HämäläinenDepartment of Medicine, Kuopio University Hospital, Kuopio.
Kaarina HeiskanenNew Children's Hospital, Pediatric Research Center, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Turku and Kuopio, Finland.
Tarja Heiskanen-KosmaDepartment of Pediatrics, Rare Diseases Unit, Kuopio University Hospital, Kuopio.
Hal M HoffmanDepartment of Pediatrics, University of California San Diego, La Jolla; Rady Children's Hospital San Diego, Division of Pediatric Allergy, Immunology, and Rheumatology, San Diego.
Luis Ignacio Gonzalez-GranadoPediatrics Department, University Hospital 12 de Octubre, Research Institute Hospital, School of Medicine Complutense University, Madrid.
Anthony L GuerrerioDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore.
Leena KainulainenDepartment of Pediatrics and Medicine, Turku University Hospital, University of Turku, Turku, Finland.
Ashish KumarCincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati.
Monica G LawrenceUniversity of Virginia Health, Charlottesville.
Carina LevinPediatric Hematology Unit, Emek Medical Centre, Afula, and the Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Timi MarteliusAdult Immunodeficiency Unit, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki.
Olaf NethPediatric Infectious Diseases, Rheumatology and Immunology Unit, Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain.
Peter OlbrichPediatric Infectious Diseases, Rheumatology and Immunology Unit, Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain.
Alejandro PalmaServicio de Immunología y Reumatología, Hospital Nacional de Pediatría Prof Dr Juan P. Garrahan, Buenos Aires.
Niraj C PatelDivision of Allergy and Immunology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta.
Tamara PozosDepartment of Clinical Immunology, Children's Minnesota, Minneapolis.
Kahn PreeceClinical Immunogenomics Research Consortium of Australasia (CIRCA); Department of Paediatric Immunology, John Hunter Children's Hospital, Newcastle (Australia).
Saúl Oswaldo Lugo ReyesImmunodeficiencies Research Unit, National Institute of Pediatrics, Coyoacan, Mexico City.
Mark A RussellUniversity of Exeter Medical School, Exeter.
Yael SchejterDepartment of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University, Jerusalem.
Christine SeroogyDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
Jan SinclairClinical Immunogenomics Research Consortium of Australasia (CIRCA); Starship Children's Hospital, Auckland.
Effie SkevofilaxDepartment of Pediatric Hematology-Oncology (TAO) and First Department of Pediatrics, Aghia Sophia Children's Hospital, Athens.
Daniel SuanClinical Immunogenomics Research Consortium of Australasia (CIRCA); Garvan Institute of Medical Research, Darlinghurst; Westmead Clinical School, University of Sydney, Westmead.
Daniel SuezAllergy, Asthma & Immunology Clinic, PA, Irving.
Paul SzabolcsUniversity of Pittsburgh Medical Center, Children's Hospital of Pittsburgh, Pittsburgh.
Helena VelascoDivision of Allergy and Clinical Immunology, Moinhos de Vento Hospital, Porto Alegre.
Klaus WarnatzInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg.
Kelly WalkovichDepartment of Pediatrics, C. S. Mott Children's Hospital, Michigan Medicine, Ann Arbor.
Austen WorthGreat Ormond Street Hospital for Children, London.
STAT3 GOF Working Group members
Mikko R J SeppänenRare Disease Center, Children's Hospital, and Adult Primary Immunodeficiency Outpatient Clinic, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki.
Troy R TorgersonAllen Institute, Seattle.
Georgios SogkasDepartment of Clinical Immunology and Rheumatology, Hannover Medical School, Hanover.
Stephan EhlInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg.
Stuart G TangyeClinical Immunogenomics Research Consortium of Australasia (CIRCA); Garvan Institute of Medical Research, Darlinghurst; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney.
Megan A CooperDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University School of Medicine, St Louis.
Joshua D MilnerDepartment of Pediatrics, Division of Allergy and Immunology, Columbia University, New York Presbyterian Hospital, New York.
Lisa R Forbes SatterDepartment of Pediatrics, Baylor College of Medicine and William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston. Electronic address: lisa.forbes@bcm.edu.
University of Freiburg · DEBaylor College of Medicine · USDominican Hospital · USStarship Children's Health · NZUniversidade Estadual de Campinas (UNICAMP) · BRUniversity of Exeter · GBUniversity of Utah · USAustralian National University · AUCharles University · CZChildren's Hospital of Philadelphia · USInstituto de Biomedicina de Sevilla · ESMarmara University · TRSt. Jude Children's Research Hospital · USUniversity of Helsinki · FIChulalongkorn University · THHeinrich Heine University Düsseldorf · DEKuopio University Hospital · FILille Inflammation Research International Center · FRMedizinische Hochschule Hannover · DENationwide Children's Hospital · US
Funding
Defining New Human Immunodeficiency and Immunodysregulation DisordersZIAAI001059 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2009 to 2025
$20.5MClinical, Immunological and Genetic Analyses of ALPS and Related Immunedysregulatory DisordersZIAAI000732 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAO, V KONETI · 2009 to 2025
$10.5MMechanisms of Combined Immunodeficiency due to DOCK8 DeficiencyR01AI128976 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI CHATILA, TALAL AMINE · 2018 to 2021
$1.4MDefining New Human Immunodeficiency and Immunodysregulation DisordersZ01AI001059 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN · 2008 to 2008
$658kIntramural NIH HHS Z01 AI001059NIAID NIH HHS R01 AI128976Wellcome Trust 207556/Z/17/Z
Abstract
backgroundIn 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.
objectiveThis pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.
methodsWe identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3.
resultsOverall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate.
conclusionSTAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.
Indexed as
Immune System DiseasesImmunologic Deficiency SyndromesAutoimmunityCell ProliferationChildCohort StudiesGain of Function MutationHumansLymphocytesMutationSTAT3 Transcription FactorSTAT3 protein, humanSTAT3 Transcription Factorautoimmunitycytopeniagain of functionimmune dysregulationimmunodeficiencylymphoproliferationprecision medicineSTAT3
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