Research on the morphological endotypes of chronic rhinosinusitis with polyps in the case of primary and recurrent polyposis

Establish possible endotypes in patients diagnosed with CRSwNP in the case of primary and recurrent nasal polyps by determining tissue cytokines, proliferation markers and antimicrobial proteins. Material obtained from 8 patients was divided into 4 cases with recurrent polyps and 4 primary ones. Samples of polyps were taken during nasal surgery. Controls were 17 tissue samples of healthy nasal mucosa. Immunohistochemical analysis was performed to detect Ki-67, β-Defensin 2, IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12. Results were determined semi-quantitatively and evaluated with the use of Mann-Whitney U test and Spearman’s rank correlation. Number of positive structures in Ki-67 (p=0.006), β-Defensin 2 (p=0.002), IL-1, IL-4, IL-6, IL-8, IL-10, IL-12 (p<0.001) was significantly increased in connective tissue of nasal polyps. Immunoreactive cells of β-Defensin 2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 (p<0.001) were significantly decreased in superficial epithelium of nasal polyps. There were no significant differences in cytokine and antimicrobial peptide expression between primary and recurrent patient groups. There was a strong positive correlation between number of β-Defensin 2 and connective tissue IL-8; connective tissue IL-1 and both connective tissue and epithelial IL-4; connective tissue IL-4 and epithelial IL-4; epithelial IL-6 and IL-8 in primary polyps. Recurrent polyps demonstrated a strong negative correlation between IL-1 and both epithelial IL-1 and IL-10; IL-6 and IL-10 as well as a strong positive correlation between epithelial IL-1 and IL-10; epithelial IL-7 and IL8. Increase in cytokine and antimicrobial peptide appearance in the connective tissue and a decrease in the epithelium of a nasal polyp indicates a significant intensification of the connective tissue immune response and stimulation of immune cell differentiation. Difference in correlating factors as well as emerging negative correlations could indicate a dysregulation of cytokine secretion in recurrent CRSwNP as the disease progresses.