TY - JOUR
T1 - STAT3 gain-of-function mutation in a patient with pulmonary Mycobacterium abscessus infection
AU - Gonzalez-Mancera, Miguel S.
AU - Johnson, Britt
AU - Mirsaeidi, Mehdi
N1 - Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in cellular proliferation, apoptosis, and differentiation. Mutations in the STAT3 gene have been associated with dysregulation of the immune system giving rise to primary immunodeficiency syndromes (PID). Clinically, patients may present with very broad manifestations, and its diagnosis is usually very challenging. Proper treatment remains unclear, and limited options are available. Methods: We report an adult male patient with long-standing history of immunodeficiency, who was found to have Mycobacterium abscessus infection. Two-hundred and seven immunogenes were sequenced using next-generation sequencing technology (NGS). Results: A STAT3 heterozygous missense pathologic variant was identified in the patient located in the transactivation domain (TA) of STAT3, associated with a gain of functionality, leading to recurrent bronchopulmonary infections, and involvement of multiple organ systems. Conclusions: Severe cases of autoimmunity should prompt for evaluation of PIDs in the setting of genetic mutations. Anti-IL-6 therapy may benefit patients with STAT3 GOF mutations. These patients should also be screened for lymphoproliferative disorders.
AB - Background: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in cellular proliferation, apoptosis, and differentiation. Mutations in the STAT3 gene have been associated with dysregulation of the immune system giving rise to primary immunodeficiency syndromes (PID). Clinically, patients may present with very broad manifestations, and its diagnosis is usually very challenging. Proper treatment remains unclear, and limited options are available. Methods: We report an adult male patient with long-standing history of immunodeficiency, who was found to have Mycobacterium abscessus infection. Two-hundred and seven immunogenes were sequenced using next-generation sequencing technology (NGS). Results: A STAT3 heterozygous missense pathologic variant was identified in the patient located in the transactivation domain (TA) of STAT3, associated with a gain of functionality, leading to recurrent bronchopulmonary infections, and involvement of multiple organ systems. Conclusions: Severe cases of autoimmunity should prompt for evaluation of PIDs in the setting of genetic mutations. Anti-IL-6 therapy may benefit patients with STAT3 GOF mutations. These patients should also be screened for lymphoproliferative disorders.
KW - Autoimmunity
KW - Gain of function
KW - Immunodeficiency
KW - Signal transducer and activator of transcription 3
UR - http://www.scopus.com/inward/record.url?scp=85086377416&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086377416&partnerID=8YFLogxK
U2 - 10.1016/j.rmcr.2020.101125
DO - 10.1016/j.rmcr.2020.101125
M3 - Article
AN - SCOPUS:85086377416
VL - 30
JO - Respiratory Medicine Case Reports
JF - Respiratory Medicine Case Reports
SN - 2213-0071
M1 - 101125
ER -