BACKGROUND: Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Little is known currently about possible distinguishing factors underlying these inflammatory differences.OBJECTIVE: To interrogate for differences between Caucasian and Japanese CRSwNP disease using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs).METHODS: We performed whole transcriptome RNA sequencing (RNA-seq) with endotype stratification of NPs from 8 Caucasian (residing in USA) and 9 Japanese (residing in Japan) patients. Reproducibility was confirmed by qPCR in an independent validation set of 46 Caucasian and 31 Japanese patients. Single-cell RNA-seq stratified key cell types for contributory transcriptional signatures.RESULTS: Unsupervised clustering analysis identified two major endotypes present within both NP cohorts, which have previously been reported at the cytokine level: 1) type 2 endotype and 2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct NP subgroups (p = 0.03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells.CONCLUSION: NPs from both racial groups harbor the same two major endotypes, which we determine are present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.
View details for DOI 10.1016/j.jaci.2021.11.017
View details for PubMedID 34863854