Development of a Disease Activity Score to Assess Treatment Success in Patients with NFKB1 Mutations

BackgroundNFKB1 encodes for the p105/p50 nuclear factor-kappa-B (NF-kB1) transcription factors. Heterozygous mutations in NFKB1 may lead to NF-kB1 insufficiency, which may result in a multiorgan disease. Here, we aimed to develop a disease activity score to assess treatment success in patients with NF-kB1 insufficiency.MethodsBased on phenotypic data of 179 patients with 77 distinct NFKB1 variants and clinical data from 41 patients with 22 distinct pathogenic NFKB1 variants, we identified the most relevant score parameters in a Leave-One-Out (LOO) analysis and developed the NFKB1-DAS. NFKB1-DAS values in patients with pathogenic variants in NFKB1 were compared to those of CTLA4-insufficient patients as a control group.ResultsPatients who spent at least one day in hospital in the last 6 months had a median NFKB1-DAS of 46% compared to 28% in patients without a hospital stay. In patients with pathogenic NFKB1 variants (n = 41), mean score values were 1.4-fold higher than in patients with CTLA4 deficiency (n = 31).DiscussionWe found the first indications that the newly developed NFKB1-DAS is able to measure disease activity. In a follow-up study, the NFKB1-DAS will be further validated and used to measure the effectiveness of treatment in a worldwide NFKB1 cohort.