AUTHOR=Vogel Tiphanie P. , Leiding Jennifer W. , Cooper Megan A. , Forbes Satter Lisa R. 

TITLE=STAT3 gain-of-function syndrome

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 10 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.770077

DOI=10.3389/fped.2022.770077

ISSN=2296-2360

ABSTRACT=STAT3 Gain of Function syndrome is a mulit-organ primary immune regulatory disorder characterized by early onset autoimmunity.  Patients present early in life most commonly with lymphoproliferation and autoimmune cytopenias.  However, progressive diseae is common and can encompass a wide range of clinical manifestations such as growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease and malignancy.  Treatment of the autoimmune and auto-inflammatory features of STAT3-GOF patients relies heavily on immunosuppression and is often challenging and fraught with complications including severe infections. Defects in the T cell compartment lead to decreased T regulatory cells which is thought to contribute to autoimmunity.  While T cell exhaustion and apopotis likely contribute to the lymphoproliferative phenotype, no direct correlation is established.  Here we review the known mechanistic and clinical characteristics of this heterogenous PIRD.