慢性鼻-鼻窦炎无鼻息肉患者的炎症内表型的机制和生物标志物。
Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps.
机构信息
Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
出版信息
J Allergy Clin Immunol. 2021 Apr;147(4):1306-1317. doi: 10.1016/j.jaci.2020.11.037. Epub 2020 Dec 14.
BACKGROUND
Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) is a common disease that is characterized by multiple inflammatory endotypes. However, the molecular mechanisms in CRSsNP are poorly understood compared with those of polypoid CRS.
OBJECTIVE
Our aim was to identify mechanisms and biomarkers associated with inflammatory endotypes underpinning CRSsNP.
METHODS
Ethmoid tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS. The gene expression profiles were determined by microarray analysis and quantitative RT-PCR, and expression of proteins was measured by ELISA and Luminex analysis.
RESULTS
Microarray found that compared with their levels of expression in control tissue, the levels of expression of 126, 241, and 545 genes were more than 3-fold and significantly elevated in CRSsNP with type 1 (T1) endotype, type 2 (T2) endotype, and type 3 (T3) endotype, respectively. Selected identified genes were confirmed by RT-PCR. Gene set enrichment analysis suggested that T1 CRSsNP was associated with IFN-γ signaling and antiviral immunity controlled by T cells (T1 and CD8), natural killer cells, and antigen-presenting cells; T2 CRSsNP was associated with STAT6 signaling and IgE-mediated activation controlled by eosinophils, mast cells, T2 cells, group 2 innate lymphoid cells, and antigen-presenting cells; and T3 CRSsNP was associated with IL-17 signaling, acute inflammatory response, complement-mediated inflammation, and infection controlled by neutrophils, T17 cells, B cells, and antigen-presenting cells. The results suggest that T1 (CXCL9 and CXCL10), T2 (eosinophilic proteins and CCL26), and T3 (CSF3) endotypic biomarkers in NLF may be able to distinguish tissue endotypes in CRSsNP.
CONCLUSIONS
Inflammatory endotypes in CRSsNP were controlled by different molecular mechanisms. NLF biomarker assays may allow for more precise and personalized medical treatments in CRS.
背景
慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）是一种常见疾病，其特征为多种炎症表型。然而，与息肉型 CRS 相比，CRSsNP 的分子机制尚不清楚。
目的
本研究旨在确定与 CRSsNP 炎症表型相关的机制和生物标志物。
方法
从对照患者和 CRS 患者中获取筛窦组织和鼻洗液（NLF）。通过微阵列分析和定量 RT-PCR 确定基因表达谱，并通过 ELISA 和 Luminex 分析测量蛋白质的表达。
结果
微阵列发现，与对照组织中的表达水平相比，126、241 和 545 个基因的表达水平分别在 T1、T2 和 T3 表型的 CRSsNP 中上调了 3 倍以上。通过 RT-PCR 验证了选定的鉴定基因。基因集富集分析表明，T1 CRSsNP 与由 T 细胞（T1 和 CD8）、自然杀伤细胞和抗原呈递细胞控制的 IFN-γ 信号和抗病毒免疫有关；T2 CRSsNP 与由嗜酸性粒细胞、肥大细胞、T2 细胞、2 型固有淋巴细胞和抗原呈递细胞控制的 STAT6 信号和 IgE 介导的激活有关；T3 CRSsNP 与由中性粒细胞、T17 细胞、B 细胞和抗原呈递细胞控制的 IL-17 信号、急性炎症反应、补体介导的炎症和感染有关。结果表明，NLF 中的 T1（CXCL9 和 CXCL10）、T2（嗜酸性粒细胞蛋白和 CCL26）和 T3（CSF3）表型生物标志物可能能够区分 CRSsNP 中的组织表型。
结论
CRSsNP 的炎症表型受不同分子机制控制。NLF 生物标志物检测可能使 CRS 更精确和个体化的治疗成为可能。
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