Immune Endotyping and Gene Expression Profile of Patients with Chronic Rhinosinusitis with Nasal Polyps in Aspirin-Exacerbated Respiratory Disease (AERD) and non-AERD Subgroups

Abstract

Abstract ‌Background: Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), are further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in AERD and non-AERD groups of patients with CRSwNP. Material and Method: In this study, 21 patients were enrolled and were categorized into AERD (N=10) and non-AERD (N=11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1β, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov–Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant. Results: The mean±SD age of the studied groups was 37±8.7 years old (21-50) for AERD, and 40.4±7.7 years old (31-52) for non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum IgE level was found to be higher in patients with AERD (p<0.05), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p=0.04), neutrophils (p=0.04), and plasma cells (p=0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p<0.01), IL4 (p<0.05), IL5 (p<0.05), and IL17 (p<0.05) were significantly higher in AERD than non-AERD groups. Conclusion: Higher levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.