INVESTIGATION OF NONINVASIVE BIOMARKERS FOR MANAGING PEDIATRIC EOE: A PILOT STUDY

Background and aims Eosinophilic esophagitis (EoE) is an emerging, chronic/recurrent inflammatory disorder of the esophagus. Diagnosing EoE can be a challenge due to its complex nature. Based on current guidelines, a diagnosis can be reached by conducting an endoscopy, taking 4-6 biopsies from different parts of the esophagus, and demonstrating ≥15 eosinophils per HPF. Diagnostic delay in EoE is typically 4-6 years, and once diagnosed, repeated endoscopic biopsies are required to monitor the activity of the disease. Currently we do not have any biomarkers for neither diagnosis or the monitoring of EoE. The goal of this study is to explore biomarkers that can aid in the diagnosis and monitoring of EoE. The ultimate goal is to eliminate/minimize the need for invasive endoscopic procedures and biopsies, mitigate potential complications associated with these procedures and anesthesia, and alleviate the financial burden and time-lost. Materials and methods The study included participants who were children and adolescents, with eosinophilic esophagitis (EoE) and without EoE, as a control group. Both groups consist of 21 participants. Clinical, endoscopic, and histologic data were collected at the time of enrollment and during subsequent follow-ups. The clinical assessment was conducted using the Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS® 2.0). Endoscopic evaluation was performed using the Endoscopic Reference Score (EREFS 0-9), while histologic evaluation was performed using the PEC (Peak of Eosinophil Count). The study assessed blood eosinophil count, serum pro-inflammatory cytokines, tissue and vascular remodeling markers, eosinophil proteins, tryptase, and immunoglobulin G4 (IgG4). Blood samples were obtained at baseline from each participant (both the patients and the control) and at each follow-up visit from the patients. The study used ROC curve analysis to determine cut-off levels, linear and logistic regression analyses to identify predictors of disease activity and treatment response at baseline and follow-up. Simple linear regression was used to determine the association between serum biomarkers and clinical activity variables, while logistic regression analyzed the relationship between categorical disease activity variables and noninvasive markers. A multivariable model was fitted, including significant biomarkers at baseline and follow-up. Results In this study, by using blood samples, nineteen potential biomarkers were analyzed to see if they could be used to diagnose or monitor the EoE. Three of them were found to be statistically significant. In the multivariate analysis, the IL-17 values showed a strong and significant predictive relationship with the clinical outcomes. The coefficients for IL-17 were 347.01 (95% CI 93.45–600.58; p =.01) and 428.86 (95% CI 198.77–658.95; p =.0001). The mean values of galectin (GAL)-10 (1.17 ± 0.44 ng/mL versus 0.91 ± 0.35 ng/mL) and transforming growth factor (TGF)-β (56,176.61 ± 26,251.29 pg/mL versus 25,997.67 ± 6611.68 pg/mL) were found to be significantly higher in EoE patients when compared to healthy controls (p =.02 and p =.0001, respectively). Conclusion This explorative study suggests that IL-17 could be a new marker for EoE activity, severity, and treatment response. GAL-10 and TGF-β values were found to be significantly higher in children with EoE, potentially aiding in diagnosis and improving patient outcomes. This study is the first step towards more extensive studies on noninvasive biomarkers in pediatric EoE diagnosis and management.