Glicoproteína-P secretada é um biomarcador não invasivo de rinossinusite crônica

Abstract

Objective: The discovery of noninvasive biomarkers of chronic rhinosinusitis (CRS) is critical to enabling our ability to provide prognostic information and targeted medical therapy. Epithelial P-glycoprotein (P-gp) is overexpressed in CRS and exists in an extracellular, secreted form. The aim of this study was to determine if concentrations of P-gp secretion are high in CRS and can be used to predict the severity of the disease. METHODS: This study was approved by the IRB (Institutional review board), which examines mucosal concentrations of P-gp in 36 patients (10 controls, 16 RSCs without nasal polyps and 10 RSCs with nasal polyps). P-gp concentrations were determined by enzyme-linked immunosorbent assay and total protein normalized (TP). Clinical disease severity indexes, including the Sinus-Nasal Outcome Test (SNOT-22) and the Lund-Mackay score, were collected in all patients. RESULTS: The concentration of secreted P-gp was significantly higher in patients with CRS versus the control group (mean ± standard deviation, 247.8 ± 224.8 vs. 102.4 ± 81.7 pg P-gp / µg TP, P = 0.022). A threshold value of 250æg / µg TP was used to differentiate low versus high secretors. High P-gp secretors with RSC (sPN and cPN, n = 9) demonstrated significantly higher SNOT-22 and Lund-Mackay scores (57.1 ± 7.9 and 13.9 ± 7.3) versus low secretory (38.3 ± 23.9 and 6.8 ± 7.3, P = 0.030 and P = 0.013, respectively) and presented a significantly higher proportion of RSCcPN (66.7%) versus P-gp secretory lowers (23 , 5%, n = 17, P = 0.046). Conclusion: P-gp secretion levels are significantly elevated in patients with CRS. The high secretion of P-gp is associated with a higher incidence of RSCcPN and confers worse subjective and objective measures of the severity of the disease. The presence of elevated P-gp secretion may therefore represent a new non-invasive CRS biomarker and could be used to predict patients who may benefit from P-gp inhibitory therapeutic strategies.