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
en 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dermatitis Atópica
/
Eosinofilia
/
Hipersensibilidad
Tipo de estudio:
Prognostic_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Turquía