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Severe allergic dysregulation due to a gain of function mutation in the transcription factor STAT6

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dc.contributor.authorBARIŞ, SAFA
dc.contributor.authorYÜCELTEN, AYŞE DENİZ
dc.contributor.authorBOZKURTLAR, EMİNE
dc.contributor.authorCİNEL, ZELİHA LEYLA
dc.contributor.authorAYDINER, ELİF
dc.contributor.authorÖZEN, AHMET OĞUZHAN
dc.contributor.authorsBARIŞ S., Benamar M., Chen Q., Catak M. C., Martínez-Blanco M., Wang M., Fong J., Massaad M. J., Sefer A. P., Kara A., et al.
dc.date.accessioned2023-03-28T06:08:59Z
dc.date.available2023-03-28T06:08:59Z
dc.date.issued2023-01-01
dc.description.abstractBackground: Inborn errors of immunity have been implicated in causing immune dysregulation, including allergic diseases. STAT6 is a key regulator of allergic responses. Objectives: This study sought to characterize a novel gain-of-function STAT6 mutation identified in a child with severe allergic manifestations. Methods: Whole-exome and targeted gene sequencing, lymphocyte characterization, and molecular and functional analyses of mutated STAT6 were performed. Results: This study reports a child with a missense mutation in the DNA binding domain of STAT6 (c.1114G>A, p.E372K) who presented with severe atopic dermatitis, eosinophilia, and elevated IgE. Naive lymphocytes from the affected patient displayed increased TH2- and suppressed TH1- and TH17-cell responses. The mutation augmented both basal and cytokine-induced STAT6 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reversed STAT6 hyperresponsiveness to IL-4, normalized TH1 and TH17 cells, suppressed the eosinophilia, and improved the patient\"s atopic dermatitis. Conclusions: This study identified a novel inborn error of immunity due to a STAT6 gain-of-function mutation that gave rise to severe allergic dysregulation. Janus kinase inhibitor therapy could represent an effective targeted treatment for this disorder.
dc.identifier.citationBARIŞ S., Benamar M., Chen Q., Catak M. C., Martínez-Blanco M., Wang M., Fong J., Massaad M. J., Sefer A. P., Kara A., et al., "Severe allergic dysregulation due to a gain of function mutation in the transcription factor STAT6", Journal of Allergy and Clinical Immunology, 2023
dc.identifier.doi10.1016/j.jaci.2023.01.023
dc.identifier.issn0091-6749
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85149876568&origin=inward
dc.identifier.urihttps://hdl.handle.net/11424/287915
dc.language.isoeng
dc.relation.ispartofJournal of Allergy and Clinical Immunology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTıp
dc.subjectYaşam Bilimleri
dc.subjectSağlık Bilimleri
dc.subjectTemel Bilimler
dc.subjectMedicine
dc.subjectLife Sciences
dc.subjectHealth Sciences
dc.subjectNatural Sciences
dc.subjectKlinik Tıp (MED)
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectKlinik Tıp
dc.subjectİmmünoloji
dc.subjectALERJİ
dc.subjectClinical Medicine (MED)
dc.subjectLife Sciences (LIFE)
dc.subjectCLINICAL MEDICINE
dc.subjectIMMUNOLOGY
dc.subjectALLERGY
dc.subjectİmmünoloji ve Alerji
dc.subjectImmunology and Allergy
dc.subjectImmunology
dc.subjectgain-of-function mutation
dc.subjectInborn errors of immunity
dc.subjectJakinibs
dc.subjectJanus kinase inhibitors
dc.subjectprimary atopic disorders
dc.subjectSTAT6
dc.titleSevere allergic dysregulation due to a gain of function mutation in the transcription factor STAT6
dc.typearticle
dspace.entity.typePublication
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local.indexed.atPUBMED
local.indexed.atSCOPUS
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