Peer-reviewedCC BY 4.0Frontiers in Immunology
Clinical manifestations of patients with STAT1 gain-of-function variants in Mexico
27 affiliations
- 1Laboratory of Immunodeficiency, National Institute of Pediatrics
- 2Department of Pediatrics, Hiroshima University Hospital
- 3Hiroshima University Graduate School of Biomedical and Health Sciences
- 4Department of Allergy and Immunology, Siglo XXI National Medical Center, Mexican Social Security Institute (IMSS)
- 5Division of Genetic Medicine and Clinical Pharmacology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- 6Division of Molecular Pathogenesis, Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center
- 7Clinical Microbiology Laboratory, National Institute of Medical Sciences and Nutrition Salvador Zubirán
- 8Infectious Diseases Department, National Institute of Medical Sciences and Nutrition Salvador Zubirán
- 9Department of Immunology, National Institute of Pediatrics
- 10Department of Immunology, Hospital Infantil de Especialidades de Chihuahua
- 11Department of Internal Medicine, Hospital General de México
- 12Department of Immunology and Allergy, Angeles Hospital
- 13Department of Immunology, Hospital de la Niñez Poblana
- 14Department of Allergy and Clinical Immunology Department, Nuevo Hospital Civil de Guadalajara “Dr. Juan I.Menchaca
- 15Department of Immunology, Unidad Médica de Alta Especialidad (UMAE) No. 25, Mexican Social Security Institute (IMSS)
- 16Department of Allergy and Clinical Immunology, UMAE “La Raza”, Mexican Social Security Institute (IMSS)
- 17Department of Immunology, Centro Médico de Occidente, Mexican Social Security Institute (IMSS)
- 18Regional Center of Allergy and Clinical Immunology, Hospital Universitario “Dr. José Eleuterio González”
- 19Université Paris Cité, Imagine Institute, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children
- 20Laboratory of Human Genetics of Infectious Diseases, University of Texas Southwestern Medical Center
- 21Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center
- 22Department of Microbiology, University of Texas Southwestern Medical Center
- 23Howard Hughes Medical Institute
- 24Center for Immunology, Allergy, and Pediatrics, Hospital Ángeles Lomas
- 25Department of Infectious Diseases, National Institute of Pediatrics
- 26Department of Mycology, National Institute of Pediatrics
- 27Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP
Abstract
Background: Germline Signal Transducer and Activator of Transcription 1 (STAT1) gain-of-function (GOF) variants enhance cellular responses to IL-27 and type I, II, and III interferons, predisposing to fungal, bacterial, and viral infections and immune dysregulation.
Methods: Mexican patients with pathogenic STAT1-GOF variants identified at referral centers were enrolled.
Results: Thirty patients from 17 kindreds were included. Fifteen variants were identified, including the novel C324W variant, confirmed as GOF by functional studies. All patients developed mucocutaneous candidiasis. Among 25 BCG-vaccinated patients, 24% developed BCG disease. According to the Graham criteria, seven patients (23%) with tuberculosis were classified as confirmed (n=1), possible (n=3), and probable (n=3) cases. Three patients developed both BCG disease and tuberculosis. Autoinflammatory and autoimmune manifestations occurred in 50% and 40%, respectively. Two patients developed infection-triggered macrophage activation syndrome. Seven patients (23%) died.
Conclusions: This cohort illustrates the broad clinical spectrum of STAT1 GOF disease, including infectious, inflammatory, autoimmune, and hematological manifestations. BCG disease and tuberculosis were observed in a subset of patients, highlighting the complexity of clinical presentation and the importance of comprehensive evaluation and follow-up.
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BibTeX
@article{covaguzman2026clinical,
title = {{Clinical manifestations of patients with STAT1 gain-of-function variants in Mexico}},
author = {Tiareth Lisset Cova-Guzmán and Satoshi Okada and Miyuki Tsumura and Patricia María O´Farrill-Romanillos and Rubén Martínez-Barricarte and Carla Marina Román-Montes and Marco Antonio Yamazaki-Nakashimada and Luisa Berenise Gámez-González and Viridiana López-Martínez and Gina Maribel Meléndez-Díaz and Carlos Gerardo Zuñiga-Lagunes and Héctor Gómez-Tello and María Enriqueta Nuñez-Nuñez and Beatriz Bayardo Gutiérrez and Aidé Tamara Staines-Boone and Saúl Oswaldo Lugo Reyes and Yuridia Salazar-Gálvez and Cristina Moctezuma-Trejo and Angélica Kathya Alaníz-Flores and Noemi Gómez-Hernández and Margarita Ortega-Cisneros and María del Carmen Zárate-Hernández and Juan Carlos Bustamante-Ogando and Camille Soudée and Jérémie Rosain and Stéphanie Boisson-Dupuis and Mélanie Migaud and Jean Laurent Casanova and Francisco Javier Espinosa-Rosales and Giancarlo Hernán Cristerna Tarrasa and Deborah Palacios-Reyes and Anne Puel and Jacinta Bustamante and Sara Espinosa-Padilla and Lizbeth Blancas Galicia},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1986964},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1986964/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical manifestations of patients with STAT1 gain-of-function variants in Mexico
AU - Tiareth Lisset Cova-Guzmán
AU - Satoshi Okada
AU - Miyuki Tsumura
AU - Patricia María O´Farrill-Romanillos
AU - Rubén Martínez-Barricarte
AU - Carla Marina Román-Montes
AU - Marco Antonio Yamazaki-Nakashimada
AU - Luisa Berenise Gámez-González
AU - Viridiana López-Martínez
AU - Gina Maribel Meléndez-Díaz
AU - Carlos Gerardo Zuñiga-Lagunes
AU - Héctor Gómez-Tello
AU - María Enriqueta Nuñez-Nuñez
AU - Beatriz Bayardo Gutiérrez
AU - Aidé Tamara Staines-Boone
AU - Saúl Oswaldo Lugo Reyes
AU - Yuridia Salazar-Gálvez
AU - Cristina Moctezuma-Trejo
AU - Angélica Kathya Alaníz-Flores
AU - Noemi Gómez-Hernández
AU - Margarita Ortega-Cisneros
AU - María del Carmen Zárate-Hernández
AU - Juan Carlos Bustamante-Ogando
AU - Camille Soudée
AU - Jérémie Rosain
AU - Stéphanie Boisson-Dupuis
AU - Mélanie Migaud
AU - Jean Laurent Casanova
AU - Francisco Javier Espinosa-Rosales
AU - Giancarlo Hernán Cristerna Tarrasa
AU - Deborah Palacios-Reyes
AU - Anne Puel
AU - Jacinta Bustamante
AU - Sara Espinosa-Padilla
AU - Lizbeth Blancas Galicia
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1986964
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1986964/full
AB - Background: Germline Signal Transducer and Activator of Transcription 1 (STAT1) gain-of-function (GOF) variants enhance cellular responses to IL-27 and type I, II, and III interferons, predisposing to fungal, bacterial, and viral infections and immune dysregulation. Methods: Mexican patients with pathogenic STAT1-GOF variants identified at referral centers were enrolled. Results: Thirty patients from 17 kindreds were included. Fifteen variants were identified, including the novel C324W variant, confirmed as GOF by functional studies. All patients developed mucocutaneous candidiasis. Among 25 BCG-vaccinated patients, 24% developed BCG disease. According to the Graham criteria, seven patients (23%) with tuberculosis were classified as confirmed (n=1), possible (n=3), and probable (n=3) cases. Three patients developed both BCG disease and tuberculosis. Autoinflammatory and autoimmune manifestations occurred in 50% and 40%, respectively. Two patients developed infection-triggered macrophage activation syndrome. Seven patients (23%) died. Conclusions: This cohort illustrates the broad clinical spectrum of STAT1 GOF disease, including infectious, inflammatory, autoimmune, and hematological manifestations. BCG disease and tuberculosis were observed in a subset of patients, highlighting the complexity of clinical presentation and the importance of comprehensive evaluation and follow-up.
SN - 1664-3224
ER -