Neutrophil Extracellular Traps as a Biomarker in Refractory Non-Type 2 CRSwNP

PURPOSE: Chronic rhinosinusitis (CRS) is classified into type 2 (T2) and non-T2 inflammation.

T2 CRS presents as a severe form, CRS with nasal polyps (CRSwNP), which often occurs with asthma as a comorbidity worldwide.

Some cases of non-T2 CRS show nasal polyposis and refractoriness, mainly in Asian countries.

However, its mechanism remains elusive.

To investigate a biomarker for the refractoriness of non-T2 CRSwNP via RNA sequencing.

METHODS: RNA sequencing by using nasal polyps (NPs) and ethmoidal mucosa (EM) from CRS subjects and uncinate tissues from controls was performed, and differentially expressed genes (DEGs) were analyzed (cutoffs: expression change > 2-fold, P < 0.01).

Immunofluorescence staining and enzyme-linked immunosorbent assay were performed.

RESULTS: We identified DEGs among T2-NP, non-T2-NP, T2-EM, non-T2-EM, and controls (NP vs. controls: 1,877 genes, EM vs. controls: 1,124 genes, T2-NP vs. controls: 1,790 genes, non-T2-NP vs. controls: 2,012 genes, T2-EM vs. controls: 740 genes, non-T2-EM vs. controls: 1,553 genes).

The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that neutrophil extracellular trap (NET) formation, systemic lupus erythematosus, and the phagosome were enriched in non-T2-NP vs. controls and non-T2-EM vs. controls.

Immunofluorescence staining confirmed that NETs were elevated in non-T2-NP.

Cytokine analysis demonstrated that NETs were significantly related to the refractoriness in non-T2-NPs.

CONCLUSIONS: This study demonstrated DEGs between T2 and non-T2 inflammation.

These results suggest that NETs may contribute to the refractoriness in non-T2-NPs and have a promise as a therapeutic strategy for patients with refractory non-T2-NP.