ArticleJournal of clinical immunology2023
Autosomal Dominant STAT6 Gain of Function Causes Severe Atopy Associated with Lymphoma.
Article in Journal of clinical immunology, 2023. 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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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Primary atopic disorders: Monogenic insights into immunity.Journal of human immunity · 2026Review
- STAT6: Multidimensional analysis from hematopoietic immune regulation to pathogenesis mechanisms and therapeutic targets in hematologic malignancies.Annals of hematology · 2026Review
- The CCL17-CCR4 Axis Is Critical for Mutant STAT6-Mediated Microenvironmental Remodeling and Therapeutic Resistance in Relapsed/Refractory Diffuse Large B-Cell Lymphoma.Cancer immunology research · 2026Article
- STAT6 gain-of-function disease: p.D519N is a new disease-causing variant that responds well to dupilumab treatment.The journal of allergy and clinical immunology. Global · 2025Article
- Pathological IgE Production in Inborn Errors of Immunity and Beyond.Immunological reviews · 2025Review
- Towards a Multi-omics Understanding of Anaphylaxis: Insights into Pathogenesis and Biomarker Identification.Clinical reviews in allergy & immunology · 2025Review
- Association of STAT6 gene polymorphism with atopic asthma among Yemeni children in Sana'a city, Yemen.BMC pediatrics · 2025Article
- Inborn errors of immunity with atopic phenotypes in the allergy and immunology clinic: a practical review.Current opinion in allergy and clinical immunology · 2025Review
- Decoding Immunobiology Through Genetic Errors of Immunity.Annual review of immunology · 2025Review
- Functional validation of a novel STAT3 'variant of unknown significance' identifies a new case of STAT3 GOF syndrome and reveals broad immune cell defects.Clinical and experimental immunology · 2025Article
- Atopic dermatitis, primary atopic disorders, and the cutaneous microbiome: current understanding of an expanding field.Frontiers in pediatrics · 2025Review
- Understanding and Managing Hyper IgE Syndromes.ImmunoTargets and therapy · 2025Review
- The genetics of hyper IgE syndromes.Frontiers in immunology · 2025Review
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- Neuroinflammation is responsible for pain in endometriosis - targeting the JAK-STAT pathway and mast cell activation.Frontiers in immunology · 2025Review
- Identification of shared and unique mechanisms of atopic dermatitis and ulcerative colitis by construction and computational analysis of disease maps.Computational and structural biotechnology journal · 2025Article
- Cannabichromene as a Novel Inhibitor of Th2 Cytokine and JAK/STAT Pathway Activation in Atopic Dermatitis Models.International journal of molecular sciences · 2024Article
- Infections in Inborn Errors of STATs.Pathogens (Basel, Switzerland) · 2024Review
- TThe Journal of allergy and clinical immunology · 2024Review
- Neuroimmune interplay during type 2 inflammation: Symptoms, mechanisms, and therapeutic targets in atopic diseases.The Journal of allergy and clinical immunology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator of Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified a novel heterozygous germline mutation STAT6 c.1255G > C, p.D419H leading to overactivity of IL-4 JAK/STAT signalling pathway, in a kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis and follicular lymphoma. STAT6 D419H expression and functional activity were compared with wild type STAT6 in transduced HEK293T cells and to healthy control primary skin fibroblasts and peripheral blood mononuclear cells (PBMC). We observed consistently higher STAT6 levels at baseline and higher STAT6 and phosphorylated STAT6 following IL-4 stimulation in D419H cell lines and primary cells compared to wild type controls. The pSTAT6/STAT6 ratios were unchanged between D419H and control cells suggesting that elevated pSTAT6 levels resulted from higher total basal STAT6 expression. The selective JAK1/JAK2 inhibitor ruxolitinib reduced pSTAT6 levels in D419H HEK293T cells and patient PBMC. Nuclear staining demonstrated increased STAT6 in patient fibroblasts at baseline and both STAT6 and pSTAT6 after IL-4 stimulation. We also observed higher transcriptional upregulation of downstream genes (XBP1 and EPAS1) in patient PBMC. Our study confirms STAT6 gain of function (GOF) as a novel monogenetic cause of early onset atopic disease. The clinical association of lymphoma in our kindred, along with previous data linking somatic STAT6 D419H mutations to follicular lymphoma suggest that patients with STAT6 GOF disease may be at higher risk of lymphomagenesis.245 words.
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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 OpenQuestion graph.