{
  "abstract": "NFKB1 encodes the p105/p50 NF-κB1 transcription factor. Heterozygous mutations in NFKB1 may lead to NFKB1 insufficiency affecting multiple organ systems. This study aimed to develop an NFKB1-Disease-Activity-Score (NFKB1-DAS), serving as a tool in future clinical trials. Based on published phenotypic data from 179 patients with 77 distinct NFKB1 variants, we drafted an initial score consisting of 42 parameters. This draft was subsequently analyzed in a multicenter cohort of 41 patients with 22 distinct pathogenic NFKB1 variants. Using a Leave-One-Out (LOO) analysis (cutoff differential value: 23.07), we identified the 21 most relevant parameters to construct the final NFKB1-DAS. Calculation of the NFKB1-DAS in 31 CTLA4-deficient patients as a comparison cohort showed higher scores in NFKB1-insufficient patients (p = 0.03 (95% CI [-0.16, -0.01]) and the NFKB1-DAS correlated with hospitalization (p = 0.01; OR 2.07 (95% CI [1.18; 3.62]). However, given the optimism bias occurring when testing the score in the cohort it was developed with and the limited case numbers, validation of the NFKB1-DAS in an unrelated cohort remains essential. Analysis of the NFKB1-DAS in patients with variants of unknown significance (VUS) in NFKB1 (n = 14) showed individual patients reaching high scores. Future studies could evaluate a possible utility of the score in assessing VUS pathogenicity. Ultimately, the proposed NFKB1-DAS represents a first step toward monitoring disease activity and treatment response in future clinical trials in NFKB1 insufficiency.",
  "abstract_shown": true,
  "affiliations": [
    "Clinic of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs- University of Freiburg, Freiburg, Germany. Katharina.thoma@uniklinik-freiburg.de.",
    "Institute for Immunodeficiency (IFI), Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany. Katharina.thoma@uniklinik-freiburg.de.",
    "Clinic of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs- University of Freiburg, Freiburg, Germany.",
    "Institute for Immunodeficiency (IFI), Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.",
    "FREEZE Biobank, Center for Biobanking, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.",
    "Department of Diagnostic and Interventional Radiology, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.",
    "Insitute of Medical Immunology, Berlin Institute of Health (BIH) & Charité University Medicine, Berlin, Germany.",
    "Doctor's Office for General Practice, Freiburg, Germany.",
    "Division of Immunology, Faculty of Medicine and Health Sciences, University Medicine Oldenburg, Oldenburg, Germany.",
    "Institute of Medical Genetics, Faculty of Medicine and Health Sciences, University Medicine Oldenburg, Oldenburg, Germany.",
    "Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.",
    "Department for Pediatrics, Stem Cell Transplantation and Immunology, Goethe University Frankfurt/Main, Frankfurt, Germany.",
    "Department for Pediatric Rheumatology and Immunology, St. Georg Clinic, ImmunDefektCentrum Leipzig (IDCL), Leipzig, Germany.",
    "Loewenpraxis and Klinik St. Anna Lucerne, Lucerne, Switzerland.",
    "Department for Infectious Diseases, University Clinic Hamburg-Eppendorf, Hamburg, Germany.",
    "Department for Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.",
    "Department for Pediatric Hematology and Oncology, Haukeland University Hospital Bergen, Bergen, Norway.",
    "Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.",
    "Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.",
    "German Center for Infection Research, Satellite Center Freiburg (DZIF), Freiburg, Germany.",
    "Clinic of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs- University of Freiburg, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.",
    "Institute for Immunodeficiency (IFI), Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.",
    "German Center for Infection Research, Satellite Center Freiburg (DZIF), Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.",
    "Centre for Integrative Biological Signalling Studies (CIBSS), Albert-Ludwigs University, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.",
    "Cluster of Excellence 2155 to Hannover Medical School, Satellite Center Freiburg, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 34,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Katharina Thoma",
      "orcid": "0000-0002-9477-2735"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Pia Hassunah"
    },
    {
      "affs": [
        3
      ],
      "name": "Manfred Fliegauf"
    },
    {
      "affs": [
        3
      ],
      "name": "Gabriele Müller"
    },
    {
      "affs": [
        3
      ],
      "name": "Andres Caballero Garcia de Oteyza"
    },
    {
      "affs": [
        3
      ],
      "name": "Pavla Mrovecova"
    },
    {
      "affs": [
        4
      ],
      "name": "Helene Kraus"
    },
    {
      "affs": [
        5
      ],
      "name": "Prerana Agarwal"
    },
    {
      "affs": [
        5
      ],
      "name": "Maximilian Frederik Russe"
    },
    {
      "affs": [
        6
      ],
      "name": "Birgit Sawitzki"
    },
    {
      "affs": [
        6
      ],
      "name": "Lev Petrov"
    },
    {
      "affs": [
        6
      ],
      "name": "Katrin Vogt"
    },
    {
      "affs": [
        3
      ],
      "name": "Nadezhda Camacho Ordonez"
    },
    {
      "affs": [
        2,
        3,
        7
      ],
      "name": "Aleksandra Hirsch"
    },
    {
      "affs": [
        2,
        3,
        8,
        9
      ],
      "name": "Christoph B Geier"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Máté Krausz"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Sigune Goldacker"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Natalie Frede"
    },
    {
      "affs": [
        3
      ],
      "name": "Stephan Ehl"
    },
    {
      "affs": [
        3
      ],
      "name": "Sarah Salou"
    },
    {
      "affs": [
        10
      ],
      "name": "Ansgar Schulz"
    },
    {
      "affs": [
        11
      ],
      "name": "Shahrzad Bakhtiar"
    },
    {
      "affs": [
        12
      ],
      "name": "Maria Fasshauer"
    },
    {
      "affs": [
        13
      ],
      "name": "Oliver Hausmann"
    },
    {
      "affs": [
        14
      ],
      "name": "Anja-Dorothee Hüfner"
    },
    {
      "affs": [
        15
      ],
      "name": "Martin Stanulla"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Anna Luijendijk"
    },
    {
      "affs": [
        17,
        18
      ],
      "name": "Faranaz Atschekzei"
    },
    {
      "affs": [
        17,
        18
      ],
      "name": "Georgios Sogkas"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ulrich Salzer"
    },
    {
      "affs": [
        3
      ],
      "name": "Baerbel Keller"
    },
    {
      "affs": [
        3,
        18
      ],
      "name": "Michele Proietti"
    },
    {
      "affs": [
        2,
        3,
        19
      ],
      "name": "Klaus Warnatz"
    },
    {
      "affs": [
        20,
        21,
        22,
        23,
        24
      ],
      "name": "Bodo Grimbacher",
      "orcid": "0000-0002-6897-6806"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6qhv5gyt3rvh8.bib",
  "cited_by": 0,
  "doi": "10.1007/s10875-026-02081-3",
  "fulltext_url": "https://europepmc.org/articles/PMC13680531",
  "id": "6qhv5gyt3rvh8",
  "issns": [
    "0271-9142",
    "1573-2592"
  ],
  "landing_url": "https://europepmc.org/article/MED/42895583",
  "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": "W7222949528",
  "pdf_url": "https://europepmc.org/articles/PMC13680531?pdf=render",
  "pmcid": "PMC13680531",
  "pmid": "42895583",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6qhv5gyt3rvh8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42895583",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42895583"
    }
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders",
      "subfield": "immunology"
    }
  ],
  "title": "A multi-composite disease activity score (NFKB1-DAS) for NFKB1 insufficiency.",
  "title_text": "A multi-composite disease activity score (NFKB1-DAS) for NFKB1 insufficiency.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/6qhv5gyt3rvh8",
  "venue": "Journal of clinical immunology",
  "versions": []
}