{
  "abstract": "Autosomal dominant STAT1 gain-of-function (GOF) is an inborn error of immunity characterized by chronic mucocutaneous candidiasis and variable immune dysregulation. JAK inhibitors are a promising therapy, but their efficacy in STAT1 GOF remains variable. We longitudinally evaluated the clinical and molecular impact of JAK inhibitors in two STAT1 GOF patients, harboring p.R321S and p.T385M mutations, using Cellular Indexing of Transcriptomes and Epitopes by sequencing, flow cytometry, cytokine measurement, and allele-specific expression analysis in peripheral blood mononuclear cells and serum. Rapid yet incomplete immune reconstitution was observed as early as 1 week after treatment initiation. T cells rebalanced to a more homeostatic status and TCR repertoire diversity increased rapidly. However, some immune defects remained, including natural killer deficiency in one patient. The pronounced transcriptional dysregulation in monocytes was not explained by an unbalanced mutant STAT1 expression but improved with JAK-inhibitor treatment. JAK inhibitors provided significant clinical and immunological benefits to STAT1 GOF patients but did not fully restore immune homeostasis. These findings highlight the therapeutic potential and limitations of JAK inhibitors in STAT1 GOF.",
  "abstract_shown": true,
  "affiliations": [
    "Advanced Disease Modelling, Targeted Drug Discovery and Gene Therapy (ADVANTAGE), Department of Pharmacological and Pharmaceutical Sciences, Faculty of Medicine, KU Leuven, Leuven, Belgium.",
    "Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium.",
    "Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium.",
    "Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.",
    "Department of Hematology, University Hospitals Leuven and Laboratory of Experimental Transplantation, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.",
    "Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.",
    "Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.",
    "Leuven Viral Vector Core, Group Biomedical Sciences, Faculty of Medicine, KU Leuven , Leuven, Belgium."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Cecilia Iglesias-Herrero",
      "orcid": "0000-0002-9863-206X"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Willem Roosens",
      "orcid": "0000-0002-6209-8045"
    },
    {
      "affs": [
        0
      ],
      "name": "Georgina Galicia",
      "orcid": "0000-0003-4316-6986"
    },
    {
      "affs": [
        1
      ],
      "name": "Jonathan Cremer",
      "orcid": "0000-0002-3793-8217"
    },
    {
      "affs": [
        3
      ],
      "name": "Pedro Elias Marques",
      "orcid": "0000-0002-5613-8012"
    },
    {
      "affs": [
        4
      ],
      "name": "Timothy Devos",
      "orcid": "0000-0002-6881-417X"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Leen Moens",
      "orcid": "0000-0002-5347-6526"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Isabelle Meyts",
      "orcid": "0000-0003-1214-0302"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Rik Gijsbers",
      "orcid": "0000-0003-0191-3904"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Rik Schrijvers",
      "orcid": "0000-0002-4261-6220"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ded54jesggh7z.bib",
  "cited_by": 0,
  "doi": "10.70962/jhi.20260009",
  "fulltext_url": "https://europepmc.org/articles/PMC13651749",
  "id": "ded54jesggh7z",
  "issns": [
    "3065-8993"
  ],
  "landing_url": "https://europepmc.org/article/MED/42853149",
  "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",
      "2403|Immunodeficiency and Autoimmune Disorders"
    ]
  ],
  "openalex": "W7221129225",
  "pdf_url": "https://europepmc.org/articles/PMC13651749?pdf=render",
  "pmcid": "PMC13651749",
  "pmid": "42853149",
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ded54jesggh7z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "MED:42853149",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42853149"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders",
      "subfield": "immunology"
    }
  ],
  "title": "JAK-inhibitor treatment induces rapid yet incomplete immune reconstitution in STAT1 gain-of-function.",
  "title_text": "JAK-inhibitor treatment induces rapid yet incomplete immune reconstitution in STAT1 gain-of-function.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/ded54jesggh7z",
  "venue": "Journal of human immunity",
  "versions": []
}