Peer-reviewedCC BYJournal of human immunity
IRF4 p.T95R combined immunodeficiency: Clinical features and transplant outcomes.
18 affiliations
- 1Department of Pediatrics, BC Children's Hospital, The University of British Columbia, Vancouver, Canada.
- 2Experimental Medicine Program, Faculty of Medicine, The University of British Columbia , Vancouver, Canada.
- 3Allergy and Immunology Service, Hospital de Niños VJ Vilela , Rosario, Argentina.
- 4Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
- 5Pediatric Immunology, Hematology and Rheumatology Department, Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
- 6Laboratory "Genome Dynamics in Human Diseases," INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
- 7Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
- 8Department of Hématologie, Necker - Enfants Malades Hospital, Assistance Publique des Hopitaux de Paris (Institut IMAGINE INSERM U1163), Université Paris Cité, Paris, France.
- 9Division of Genetic Medicine and Clinical Pharmacology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
- 10Division of Molecular Pathogenesis, Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA.
- 11Immunology Service, Hospital de Especialidades Unidad Médica de Alta Especialidad, 25 del Instituto Mexicano del Seguro Social , Monterrey, México.
- 12Pediatric Allergy and Immunology Department, Dr Ovidio Aliaga Uría Children's Hospital, La Paz, Bolivia.
- 13Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris , Paris, France.
- 14Université Paris Cité, Institut Imagine, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France.
- 15Pediatric Allergy Immunology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
- 16Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
- 17Institute for Transfusion Medicine, University of Ulm , Ulm, Germany.
- 18Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm , Ulm, Germany.
Abstract
IRF4 is a transcription factor within the interferon regulatory factor family that controls key aspects of lymphocyte differentiation and adaptive immunity. The heterozygous IRF4 p.Thr95Arg (p.T95R) variant affecting the DNA-binding domain was recently identified to cause a new inborn error of immunity, but the longitudinal clinical course and therapeutic implications remain incompletely defined. We performed detailed clinical characterization and follow-up of all 10 known patients. Each presented with early-onset combined immunodeficiency characterized by hypo- or agammaglobulinemia and marked susceptibility to opportunistic infections. Pulmonary disease was universal, and gastrointestinal involvement was associated with a more severe clinical course. Four patients underwent hematopoietic stem cell transplantation; two survived, and two died. Notably, both deaths occurred in patients transplanted in the setting of active infection. These findings define IRF4 p.T95R as a profound combined immunodeficiency with high infectious burden and demonstrate that disease severity and intervention timing may contribute to transplant outcomes, supporting early diagnosis and timely transplantation before uncontrolled infection.
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BibTeX
@article{stojcic2026irf4,
title = {{IRF4 p.T95R combined immunodeficiency: Clinical features and transplant outcomes.}},
author = {Mattison P Stojcic and Makenzie A Manning and Miguel Galicchio and Manfred Hönig and Despina Moshous and Sven Kracker and Felipe Suarez and Ruben Martinez-Barricarte and Aidé Tamara Staines-Boone and Yuridia Salazar Gálvez and Edgar-Domingo Cordero-Chura and Estefany-Graciela Mamani-Velasquez and Jian Cui and Jeremie Rosain and Pandiarajan Vignesh and Sergio D Rosenzweig and Klaus Schwarz and Catherine M Biggs and Jacob Rozmus and Stuart E Turvey},
journal = {Journal of human immunity},
year = {2026},
month = oct,
doi = {10.70962/jhi.20260069},
url = {https://europepmc.org/article/MED/42853148},
note = {CC BY},
}
RIS
TY - JOUR
TI - IRF4 p.T95R combined immunodeficiency: Clinical features and transplant outcomes.
AU - Mattison P Stojcic
AU - Makenzie A Manning
AU - Miguel Galicchio
AU - Manfred Hönig
AU - Despina Moshous
AU - Sven Kracker
AU - Felipe Suarez
AU - Ruben Martinez-Barricarte
AU - Aidé Tamara Staines-Boone
AU - Yuridia Salazar Gálvez
AU - Edgar-Domingo Cordero-Chura
AU - Estefany-Graciela Mamani-Velasquez
AU - Jian Cui
AU - Jeremie Rosain
AU - Pandiarajan Vignesh
AU - Sergio D Rosenzweig
AU - Klaus Schwarz
AU - Catherine M Biggs
AU - Jacob Rozmus
AU - Stuart E Turvey
PY - 2026
DA - 2026/10/09
JO - Journal of human immunity
DO - 10.70962/jhi.20260069
UR - https://europepmc.org/article/MED/42853148
AB - IRF4 is a transcription factor within the interferon regulatory factor family that controls key aspects of lymphocyte differentiation and adaptive immunity. The heterozygous IRF4 p.Thr95Arg (p.T95R) variant affecting the DNA-binding domain was recently identified to cause a new inborn error of immunity, but the longitudinal clinical course and therapeutic implications remain incompletely defined. We performed detailed clinical characterization and follow-up of all 10 known patients. Each presented with early-onset combined immunodeficiency characterized by hypo- or agammaglobulinemia and marked susceptibility to opportunistic infections. Pulmonary disease was universal, and gastrointestinal involvement was associated with a more severe clinical course. Four patients underwent hematopoietic stem cell transplantation; two survived, and two died. Notably, both deaths occurred in patients transplanted in the setting of active infection. These findings define IRF4 p.T95R as a profound combined immunodeficiency with high infectious burden and demonstrate that disease severity and intervention timing may contribute to transplant outcomes, supporting early diagnosis and timely transplantation before uncontrolled infection.
SN - 3065-8993
ER -