Severe allergic dysregulation due to a gain of function mutation in the transcription factor STAT6.
J Allergy Clin Immunol
; 152(1): 182-194.e7, 2023 07.
Article
em En
| MEDLINE
| ID: mdl-36758835
ABSTRACT
BACKGROUND:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dermatite Atópica
/
Eosinofilia
/
Hipersensibilidade
Tipo de estudo:
Prognostic_studies
Limite:
Child
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article