Evidence map›Paper›PMID 42061468›Full record

Observational studyThe Journal of allergy and clinical immunology2026

Clinical features, genetics, treatment, and long-term outcomes of STAT3 hyper-IgE syndrome: Single-center cohort analysis.

Alexandra F Freeman, Chen Wang, Amanda Urban, Iris Martin, Lauren Dang, Joie Davis, Jenna R E Bergerson, Sania Ali, Zixiao Annie An, Meera Patel and 39 more

Registry-linked trialAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Journal of allergy and clinical immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00006150 (Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT00006150 recruitingnot on this map

Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2000Enrolled600ConditionsInfections, Pneumonia, Immune System Diseases, STAT3 Transcription Factor
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

49 authors.

Alexandra F FreemanLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md. Electronic address: freemaal@mail.nih.gov.
Chen WangLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Amanda UrbanClinical Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, Md.
Iris MartinLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Lauren DangBiostatistics Research Branch, NIAID, NIH, Bethesda, Md.
Joie DavisLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Jenna R E BergersonLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Sania AliLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Zixiao Annie AnLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Meera PatelLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Hastings WilliamsonLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Beatriz E MarcianoLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Christine LafeerLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Susan RoyLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Jean UlrickLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Theo HellerTranslational Hepatology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, Md.
Disha SharmaDigestive Diseases Branch, NIDDK, Bethesda, Md.
Leslie Castelo-SoccioDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Md.
Edward W CowenDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Md.
Heidi H KongCutaneous Microbiome and Inflammation Section, Dermatology Branch, NIAMS, NIH, Bethesda, Md.
Sarthak GuptaLupus Clinical Trials Unit, NIAMS, NIH, Bethesda, Md.
Rajarshi GhoshCentralized Sequencing Program, NIAID, NIH, Bethesda, Md.
Bryce A SeifertCentralized Sequencing Program, NIAID, NIH, Bethesda, Md.
Mari J TokitaCentralized Sequencing Program, NIAID, NIH, Bethesda, Md.
Magdalena A WalkiewiczCentralized Sequencing Program, NIAID, NIH, Bethesda, Md.
Morgan SimilukCentralized Sequencing Program, NIAID, NIH, Bethesda, Md.
Jennifer StoddardImmunology Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Md.
Sergio D RosenzweigImmunology Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Md.
Jatin Raj MattaBiomedical and Metabolic Imaging Branch, NIDDK, NIH, Bethesda, Md.
Ahmed M GharibBiomedical and Metabolic Imaging Branch, NIDDK, NIH, Bethesda, Md.
Golnar JahanmirDental Clinic, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Md.
Laurie BrenchleyDental Clinic, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Md; Laboratory of Host Immunity and Microbiome, NIAID, NIH, Bethesda, Md.
Kalpakam ShastriDental Clinic, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Md.
Niki M MoutsopoulosLaboratory of Host Immunity and Microbiome, NIAID, NIH, Bethesda, Md.
Takashi KitaniNational Institute of Neurologic Disorders and Stroke, NIH, Bethesda, Md.
Danielle E ArnoldImmune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md.
Dimana DimitrovaCenter for Immuno-Oncology, National Cancer Institute, NIH, Bethesda, Md.
Corina E GonzalezImmune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md.
Sung-Yun PaiImmune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md.
Harry L MalechLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
John I GallinLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Kevin FennellyLaboratory of Chronic Airway Infection, National Heart, Lung, and Blood Institute, NIH, Bethesda, Md.
Kenneth N OlivierDivision of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina, Chapel Hill, NC.
Joseph MackieGarvan Institute of Medical Research, Darlinghurst, Australia; School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, Australia.
Stuart G TangyeGarvan Institute of Medical Research, Darlinghurst, Australia; School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, Australia.
Amy P HsuLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.
Joshua D MilnerDivision of Pediatric Allergy, Immunology and Rheumatology, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY.
Jennifer HeimallDivision of Allergy Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pa.
Steven M HollandLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Primary Immune Deficiency ClinicZIAAI001247 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FREEMAN, ALEXANDRA · 2019 to 2025
$8.7M
Intramural NIH HHS Z99 AI999999Intramural NIH HHS ZIA AI001247NIH HHS 75N91019D00024
6 · The paper itself

Abstract

backgroundSignal transducer and activator of transcription 3 hyper-IgE syndrome (STAT3-HIES) is a multisystem disorder with both immunologic and nonimmunologic manifestations.

objectiveWe sought to characterize the spectrum of clinical manifestations, genetics, treatment approaches, and long-term outcomes of patients with STAT3-HIES.

methodsClinical features, laboratory findings, treatment, and survival were reviewed in the largest single-center STAT3-HIES cohort (n = 164) prospectively followed under a natural history protocol (NCT00006150).

resultsIn addition to the classic skin, lung, dental, and musculoskeletal manifestations captured in the 1999 scoring system, we comprehensively characterized disease phenotypes across multiple organ systems, including previously underrecognized features. Lung disease remained the major morbidity with both infectious and parenchymal complications. During longitudinal follow-up, age-related vascular and skeletal degeneration emerged and significantly affected quality of life in patients 45 years and older. No genotype-phenotype correlations were identified. In terms of management, optimal supportive measures, including antimicrobials and immunoglobulin replacement therapy, tailored to disease features and individual risk factors, remained the primary approach. Dupilumab was used primarily for the eczematous dermatitis and demonstrated significant clinical benefit. In highly selected cases (n = 6), allogeneic hematopoietic stem cell transplantation was performed and showed reduction in infection burden. The median overall survival was 55 years-significantly shorter than that of the general United States population-and was not affected by sex, variant location, or proband status.

conclusionsSTAT3-HIES is a multisystem disorder that requires multidisciplinary care. Early diagnosis and supportive measures have altered its natural history. Recognition and improved understanding of the nonimmunologic manifestations of this disorder will further improve patient outcomes.

Indexed as

Job SyndromeSTAT3 Transcription FactorAdolescentAdultChildChild, PreschoolCohort StudiesFemaleHumansMaleMiddle AgedPhenotypeTreatment OutcomeYoung AdultSTAT3 protein, humanSTAT3 Transcription Factoraginghyper-IgE syndromenatural historyphenotypeSTAT3

Identifiers

PMID42061468
PMCPMC13310521

What Socratic holds

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Registered trials

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 Socratic graph.