A multi-composite disease activity score (NFKB1-DAS) for NFKB1 insufficiency.

@article{thoma2026multicomposite,
  title = {{A multi-composite disease activity score (NFKB1-DAS) for NFKB1 insufficiency.}},
  author = {Katharina Thoma and Pia Hassunah and Manfred Fliegauf and Gabriele Müller and Andres Caballero Garcia de Oteyza and Pavla Mrovecova and Helene Kraus and Prerana Agarwal and Maximilian Frederik Russe and Birgit Sawitzki and Lev Petrov and Katrin Vogt and Nadezhda Camacho Ordonez and Aleksandra Hirsch and Christoph B Geier and Máté Krausz and Sigune Goldacker and Natalie Frede and Stephan Ehl and Sarah Salou and Ansgar Schulz and Shahrzad Bakhtiar and Maria Fasshauer and Oliver Hausmann and Anja-Dorothee Hüfner and Martin Stanulla and Anna Luijendijk and Faranaz Atschekzei and Georgios Sogkas and Ulrich Salzer and Baerbel Keller and Michele Proietti and Klaus Warnatz and Bodo Grimbacher},
  journal = {Journal of clinical immunology},
  year = {2026},
  month = oct,
  doi = {10.1007/s10875-026-02081-3},
  url = {https://europepmc.org/article/MED/42895583},
  note = {CC BY},
}

TY  - JOUR
TI  - A multi-composite disease activity score (NFKB1-DAS) for NFKB1 insufficiency.
AU  - Katharina Thoma
AU  - Pia Hassunah
AU  - Manfred Fliegauf
AU  - Gabriele Müller
AU  - Andres Caballero Garcia de Oteyza
AU  - Pavla Mrovecova
AU  - Helene Kraus
AU  - Prerana Agarwal
AU  - Maximilian Frederik Russe
AU  - Birgit Sawitzki
AU  - Lev Petrov
AU  - Katrin Vogt
AU  - Nadezhda Camacho Ordonez
AU  - Aleksandra Hirsch
AU  - Christoph B Geier
AU  - Máté Krausz
AU  - Sigune Goldacker
AU  - Natalie Frede
AU  - Stephan Ehl
AU  - Sarah Salou
AU  - Ansgar Schulz
AU  - Shahrzad Bakhtiar
AU  - Maria Fasshauer
AU  - Oliver Hausmann
AU  - Anja-Dorothee Hüfner
AU  - Martin Stanulla
AU  - Anna Luijendijk
AU  - Faranaz Atschekzei
AU  - Georgios Sogkas
AU  - Ulrich Salzer
AU  - Baerbel Keller
AU  - Michele Proietti
AU  - Klaus Warnatz
AU  - Bodo Grimbacher
PY  - 2026
DA  - 2026/10/19
JO  - Journal of clinical immunology
DO  - 10.1007/s10875-026-02081-3
UR  - https://europepmc.org/article/MED/42895583
AB  - 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.
SN  - 0271-9142
SN  - 1573-2592
ER  -