Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps

Abstract Background Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) is a common disease and is characterized by multiple inflammatory endotypes. However, molecular mechanisms in CRSsNP are poorly understood compared to polypoid CRS. Objective To identify mechanisms and biomarkers associated with inflammatory endotypes underpinning CRSsNP. Methods Ethmoid tissues and nasal lavage fluids (NLF) were obtained from control patients and patients with CRS. The gene expression profiles were determined by microarray as well as quantitative RT-PCR and expression of proteins was measured by ELISA and Luminex. Results Microarray found that 126, 241, and 545 genes were >3-fold and significantly elevated in CRSsNP with type (T) 1 endotype (T1 CRSsNP), T2 CRSsNP, and T3 CRSsNP, respectively, compared to control tissue. Selected identified genes were confirmed by RT-PCR. Gene set enrichment analysis suggested that T1 CRSsNP was associated with IFN-γ-signaling and anti-viral immunity controlled by T cells (Th1 and CD8+), NK cells and antigen presenting cells (APC); T2 CRSsNP was associated with STAT6-signaling and IgE-mediated activation controlled by eosinophils, mast cells, Th2 cells, ILC2 and APC; and T3 CRSsNP was associated with IL-17-signaling, acute-inflammatory response, complement-mediated inflammation and infection controlled by neutrophils, Th17 cells, B cells and APC. 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.