O impacto da neurotoxina derivada de eosinófilos no diagnóstico da esofagite eosinofílica em pacientes pediátricos

Abstract

Introduction: Eosinophilic Esophagitis (EoE) as an emerging clinical entity presents challenges in its clinical management. Overlapping signs and symptoms with other gastrointestinal disorders present in childhood, such as gastroesophageal reflux disease (GERD), make diagnosis more difficult and delay therapeutic approach. Objective: The aim of this study was to identify and validate a biomarker for EoE through biological samples from pediatric patients undergoing diagnostic upper digestive endoscopy. Methods: Consecutive patients were included in a pediatric endoscopic cohort. Symptom, endoscopic and histological scores were performed for clinical characterization. Tissue and esophageal mucus samples were obtained during the endoscopic procedure. Patients were classified as EoE, GERD or controls during the clinical follow-up. Proteomics were applied to select candidate proteins for the biomarker. Tissue immunohistochemistry (IHC) and mucus ELISA were used to validate the biomarker in samples of the cohort. Results: One hundred and ten eligible children underwent the endoscopic procedure, 3 were lost during follow-up, 16 classified as EoE (14.5%), 14 as GERD (12.5%) and 77 as controls (70%). Proteomic analysis identified eosinophil-derived neurotoxin (EDN, RNase2) as the best biomarker for EoE. Endoscopic, histological, and tissue IHC scores differed between the EoE and control groups (P <0.0001). Only the histological score differed between the EoE and GERD groups (P = 0.0007). The presence of NDE in esophageal mucus differentiated the EoE and GERD groups (0.515 ± 0.402 vs 0.186 0.125, P = 0.0066), and EoE and controls (0.515 ± 0.402 vs 0.177 ± 0.194, P <0.0002). NDE in mucus was highly correlated with peak eosinophil count (PEC) in esophageal tissue. Conclusion: The diagnosis of EoE was significantly optimized by detecting NDE in tissue and esophageal mucus in pediatric patients with accuracy of 90% and 78%, respectively. The evaluation of NDE in patients with suspected endoscopic and histological scores for EoE can be considered a useful tool in the differential diagnosis.