Jo Ara, Lim Hee-Suk, Eun Kyoung Mi, Park Jin-A, Hong Seung-No, Kim Dae Woo
Department of Otorhinolaryngology-Head & Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, Korea.
Allergy Asthma Immunol Res. 2024 Sep;16(5):473-489. doi: 10.4168/aair.2024.16.5.473.
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.
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, < 0.01). Immunofluorescence staining and enzyme-linked immunosorbent assay were performed.
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.
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.
慢性鼻-鼻窦炎（CRS）分为2型（T2）炎症和非T2炎症。T2型CRS表现为严重形式，即伴鼻息肉的CRS（CRSwNP），在全球范围内常与哮喘合并发生。部分非T2型CRS病例表现为鼻息肉病且具有难治性，主要见于亚洲国家。然而，其机制仍不清楚。通过RNA测序研究非T2型CRSwNP难治性的生物标志物。
对CRS患者的鼻息肉（NP）和筛窦黏膜（EM）以及对照的钩突组织进行RNA测序，并分析差异表达基因（DEG）（截断值：表达变化>2倍，<0.01）。进行免疫荧光染色和酶联免疫吸附测定。
我们在T2-NP、非T2-NP、T2-EM、非T2-EM和对照之间鉴定出DEG（NP与对照：1877个基因，EM与对照：1124个基因，T2-NP与对照：1790个基因，非T2-NP与对照：2012个基因，T2-EM与对照：740个基因，非T2-EM与对照：1553个基因）。京都基因与基因组百科全书（KEGG）通路分析显示，与对照相比，非T2-NP和非T2-EM中中性粒细胞胞外陷阱（NET）形成、系统性红斑狼疮和吞噬体通路富集。免疫荧光染色证实非T2-NP中NET升高。细胞因子分析表明，NET与非T2-NP的难治性显著相关。
本研究证明了T2和非T2炎症之间的DEG。这些结果表明，NET可能导致非T2-NP的难治性，有望成为难治性非T2-NP患者的治疗策略。
