D3.10 - An exploratory assessment of biological inflammatory markers found in nasal epithelial cells from rhinitic patients as prospective predictors of rhinitis exacerbation status
Background
Persistent rhinitis, both allergic (AR) and non-allergic (NAR), represents a significant socioeconomic burden and impairs patients' quality of life. Th2 responses have been associated with disease. However, the essential role of nasal epithelial cells (NECs) in immune responses is recognized today. NEC acts as a primary barrier against viruses, bacteria, environmental particles, and allergens such as house dust mites (Dermatophagoides pteronyssinus) (HDM). Furthermore, NECs' secretion of functional molecules is essential for an accurate immune response. In this way, unexplored molecules (biomarkers) secreted by NECs may play a pivotal role in inflammatory homeostasis, and their expression may be dysregulated in NECs from patients with rhinitis. Then, identifying unexplored biomarkers and assessing their expression in patients will be relevant for understanding rhinitis pathophysiology and for establishing the clinical status of the disease.
Method
To identify unexplored biomarkers, we generate physiologically functional 3D nasal epithelium from primary NECs obtained by nasal brush from AR (n=9), NAR (n=8), and healthy people (n=4). Epithelium were stimulated with HDM for 12 hours. Then, 21,448 gene expression analysis was performed using the Affymetrix Clarion S array. To assess differential expression, all genes that statistically significantly upregulated or downregulated their expression by at least two-fold were selected.
Results
: 8 genes were upregulated, and 16 were downregulated in the epithelium of AR patients. mRNA expression of all 24 genes differentially expressed were assess individually by qPCR. This validation showed significant downregulation of Prolyne dehydrogenase (PRODH) gene expression in patients with AR compared to NAR patients and healthy individuals. Since RNA does not necessarily reflect protein expression, we used the primary anti-PRODH antibody (A-11) to examine PRODH protein expression in epithelium among those involved. Immunohistochemically assess reported a significant reduction in PRODH protein expression in the epithelium of AR patients.
Conclusion
PRODH protein expression is significantly reduced in the epithelium of AR patients. These findings would provide us a potential diagnostic tool to optimize rhinitis treatment and management. It is necessary to increase the number of patients to validate these results. New studies are needed to explore the role of PRODH in rhinitis pathophysiology.
