{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, BC Children's Hospital, The University of British Columbia, Vancouver, Canada.",
    "Experimental Medicine Program, Faculty of Medicine, The University of British Columbia , Vancouver, Canada.",
    "Allergy and Immunology Service, Hospital de Niños VJ Vilela , Rosario, Argentina.",
    "Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.",
    "Pediatric Immunology, Hematology and Rheumatology Department, Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.",
    "Laboratory \"Genome Dynamics in Human Diseases,\" INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.",
    "Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.",
    "Department of Hématologie, Necker - Enfants Malades Hospital, Assistance Publique des Hopitaux de Paris (Institut IMAGINE INSERM U1163), Université Paris Cité, Paris, France.",
    "Division of Genetic Medicine and Clinical Pharmacology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.",
    "Division 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.",
    "Immunology Service, Hospital de Especialidades Unidad Médica de Alta Especialidad, 25 del Instituto Mexicano del Seguro Social , Monterrey, México.",
    "Pediatric Allergy and Immunology Department, Dr Ovidio Aliaga Uría Children's Hospital, La Paz, Bolivia.",
    "Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris , Paris, France.",
    "Université Paris Cité, Institut Imagine, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Paris, France.",
    "Pediatric Allergy Immunology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.",
    "Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.",
    "Institute for Transfusion Medicine, University of Ulm , Ulm, Germany.",
    "Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm , Ulm, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mattison P Stojcic",
      "orcid": "0009-0006-3281-3921"
    },
    {
      "affs": [
        0
      ],
      "name": "Makenzie A Manning",
      "orcid": "0009-0003-7020-2097"
    },
    {
      "affs": [
        2
      ],
      "name": "Miguel Galicchio",
      "orcid": "0000-0002-9765-3424"
    },
    {
      "affs": [
        3
      ],
      "name": "Manfred Hönig",
      "orcid": "0000-0001-9165-1690"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Despina Moshous",
      "orcid": "0000-0001-6719-3693"
    },
    {
      "affs": [
        6
      ],
      "name": "Sven Kracker",
      "orcid": "0000-0003-4543-8236"
    },
    {
      "affs": [
        7
      ],
      "name": "Felipe Suarez",
      "orcid": "0000-0002-3537-9052"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Ruben Martinez-Barricarte",
      "orcid": "0000-0001-7925-449X"
    },
    {
      "affs": [
        10
      ],
      "name": "Aidé Tamara Staines-Boone",
      "orcid": "0000-0003-0776-8162"
    },
    {
      "affs": [
        10
      ],
      "name": "Yuridia Salazar Gálvez",
      "orcid": "0009-0009-1059-2971"
    },
    {
      "affs": [
        11
      ],
      "name": "Edgar-Domingo Cordero-Chura",
      "orcid": "0009-0002-3770-7459"
    },
    {
      "affs": [
        11
      ],
      "name": "Estefany-Graciela Mamani-Velasquez",
      "orcid": "0000-0001-7122-9134"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Jian Cui",
      "orcid": "0000-0002-8483-9975"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "Jeremie Rosain",
      "orcid": "0000-0002-2822-161X"
    },
    {
      "affs": [
        14
      ],
      "name": "Pandiarajan Vignesh",
      "orcid": "0000-0001-8490-5584"
    },
    {
      "affs": [
        15
      ],
      "name": "Sergio D Rosenzweig",
      "orcid": "0000-0002-5550-9678"
    },
    {
      "affs": [
        16,
        17
      ],
      "name": "Klaus Schwarz",
      "orcid": "0000-0003-3178-5990"
    },
    {
      "affs": [
        0
      ],
      "name": "Catherine M Biggs",
      "orcid": "0000-0002-4363-2660"
    },
    {
      "affs": [
        0
      ],
      "name": "Jacob Rozmus",
      "orcid": "0000-0003-4036-2105"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Stuart E Turvey",
      "orcid": "0000-0003-1599-1065"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0fzvs13p4nvfd.bib",
  "cited_by": 0,
  "doi": "10.70962/jhi.20260069",
  "fulltext_url": "https://europepmc.org/articles/PMC13651748",
  "id": "0fzvs13p4nvfd",
  "issns": [
    "3065-8993"
  ],
  "landing_url": "https://europepmc.org/article/MED/42853148",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": "https://europepmc.org/articles/PMC13651748?pdf=render",
  "pmcid": "PMC13651748",
  "pmid": "42853148",
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0fzvs13p4nvfd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "MED:42853148",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42853148"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "journal-openalex:2403|Immunodeficiency and Autoimmune Disorders",
      "subfield": "immunology"
    }
  ],
  "title": "IRF4 p.T95R combined immunodeficiency: Clinical features and transplant outcomes.",
  "title_text": "IRF4 p.T95R combined immunodeficiency: Clinical features and transplant outcomes.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/0fzvs13p4nvfd",
  "venue": "Journal of human immunity",
  "versions": []
}