Scoring Thoracic CT Scans of Patients with NFKB1-Related Disease for Clinical Management and Treatment Studies Using Four Parameters (Adapted from the Hartmann Score)

Background NFKB1 encodes the p105/p50 nuclear factor-kappa-B (NF-κB1) transcription factor. Heterozygous mutations in NFKB1 are associated with NFKB1-related disease, including granulomatous-lymphocytic interstitial lung disease (GLILD) or similar lung involvement. We aimed to characterize and score the severity of these pathologies in CT scans for the first time. Methods We evaluated clinical data and CT scans of 28 patients with 25 distinct NFKB1 variants (20 pathogenic and 8 variants of unknown significance [VUS]). CT scans were assessed by an experienced radiologist using the Hartmann and the modified Bhalla score. Results 15 of 20 patients with pathogenic NFKB1 variants showed pathological findings in their baseline CT. Three major phenotypes were identified: Slight bronchial wall thickening (n = 6), nodular phenotype (common variable immunodeficiency [CVID]-like) (n = 6), and bronchiectatic type (n = 3). Four parameters adapted from the Hartmann score were chosen to represent these qualities: Ground-glass opacities and consolidation (%), perilymphatic nodules (number), reticulation (%), and bronchial wall thickening (in relation to vessel diameter). The nodular type was not present in patients with a VUS in NFKB1, but a broad-spectrum of other pathological patterns. Discussion We identified three major radiological phenotypes in our NFKB1 cohort. The four parameters presented to analyze thoracic CT scans are currently validated in an unrelated worldwide NFKB1 cohort and can be used for clinical management and treatment evaluation.