Transcriptomic Profiling Reveals Differences in Mucosal Defense and Ciliary Gene Expression in Eosinophilic Nasal...

Elevated immunoglobulin (Ig) E has been frequently observed in eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP). However, the relationship between IgE levels and immune microenvironment remains poorly understood. This study aimed to characterize the transcriptomic and immunologic profiles associated with different IgE levels in eCRSwNP, and to explore their potential clinical and biological significance.

We enrolled 30 patients with eCRSwNP and stratified them into IgE-high (tissue total IgE ≥ 34.55 kU/L and serum total IgE ≥ 100 kU/L, n = 18) and IgE-low (below both thresholds, n = 12) groups. Healthy nasal mucosa from 10 control subjects was included. Bulk RNA sequencing, gene ontology (GO), KEGG pathway analysis, and immunohistochemistry were performed to characterize IgE-associated transcriptional and protein expression profiles in nasal polyp tissues.

Compared with controls, IgE-high patients exhibited higher tissue-specific IgE levels against aeroallergens, more severe clinical manifestations, and greater asthma comorbidity. Transcriptomic profiling revealed distinct gene expression patterns between eCRSwNP and healthy mucosa, with enrichment of T2 inflammation markers (CCL13, POSTN, IL5, IGHG4, and IGHE). IgE-high polyps demonstrated mucus hypersecretion and increased antimicrobial peptide expression (ITLN1, LTF, LYZ), alongside downregulated ciliary function-related genes. Immunohistochemistry validated increased IgE, IgG4, CD79a⁺ B cells and reduced FOXJ1⁺ ciliated cells in IgE-high tissues, consistent with the transcriptomic findings.

Tissue IgE levels delineate clinically and transcriptionally distinct eCRSwNP endotypes. IgE-high nasal polyps demonstrated epithelial barrier dysfunction, mucus overproduction, and antimicrobial peptide activation, highlighting the potential of IgE-based stratification to guide personalized treatment strategies in eCRSwNP.