Background: Since the coronavirus disease 2019 pandemic, local immune responses in the nasal mucosa have become an area of growing research interest. In this context, studies using noninvasive nasal brushing (NB) samples have increased markedly. However, it remains unclear whether NB samples accurately reflect the immune landscape of the nasal tissue (NT). Objective: A study was conducted to directly compare the cellular composition and immune cell responses of NB and NT samples. Methods: Paired NB and NT samples were collected from the same anatomic site. The frequency, phenotype, and effector functions of epithelial and immune cells were analyzed by single-cell RNA sequencing and flow cytometry. Results: NB samples contained a significantly higher proportion of epithelial cells than NT samples, while fibroblasts, endothelial cells, and B cells were significantly less abundant. Within the epithelial compartment, NB showed an enrichment of ciliated and secretory cells, whereas basal cells were less frequent and glandular basal/secretory cells were rarely detected. Additionally, CD103+ tissue-resident memory T cells and CD56bright natural killer cells were more abundant in NB samples than in NT samples. Functional analyses revealed distinct T-cell effector profiles between the two sample types. Notably, severe acute respiratory syndrome coronavirus 2-specific T cells were significantly less frequent in NB samples than in NT. Conclusions: NB is well suited for sampling cells located near the epithelial surface but captures fewer cells from deeper mucosal layers. Additionally, NB samples display distinct T-cell effector profiles and virus-specific T-cell frequencies compared with NT. These findings highlight the importance of selecting sampling methods that align with the specific objectives of a study. (J Allergy Clin Immunol 2026;158:278-90.)
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
Autoimmune lymphoproliferative syndrome (ALPS) is an immune-mediated disorder caused by defects affecting the FAS-mediated apoptotic pathway, particularly FAS, FASLG and FADD. Other defects in this pathway including CASP8, and CASP10, may cause overlapping phenotypes but are not uniformly classified as classical ALPS. While FAS mutations are well-documented, data on the rarer ALPS subtypes remain limited. This study systematically evaluated 31 individuals, identified by next-generation sequencing, with defects affecting the Fas-mediated apoptotic pathway by analysing their molecular, clinical, and immunological features. FAS variants accounted for 41.93
Inborn Errors of Immunity (IEI) are genetically heterogeneous diseases with nonspecific clinical presentations, often resulting in delayed diagnosis. While whole-exome sequencing (WES) is widely used for diagnosing IEI, its real-world performance in the pediatric Chinese population remains understudied. This study retrospectively analyzed 243 children aged 0 to 15 years suspected of having IEI at a single center. All underwent WES combined with copy number variant (CNV) detection. Candidate variants were initially screened using the TGex platform and validated via Sanger sequencing. Variants were classified based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) 2015 guidelines, with only those listed as P/LP variants in genes included in the IUIS 2024 IEI list considered diagnostic. In this region with a concentrated Zhuang ethnic minority population, 77 (31.69
