High-Resolution Esophageal Manometry and Tissue Proteomics Identify Candidate Biomarkers Associated with Proton Pump Inhibitor Responsiveness in Eosinophilic Esophagitis

Background: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by esophageal dysfunction and eosinophilic inflammation. Intrabolus pressure (IBP), measured by high-resolution manometry (HRM), has emerged as a potential marker for distinguishing patients who respond to proton pump inhibitors (PPIs) from those with early fibrotic changes and poor therapeutic response. This study aimed to identify tissue biomarkers predictive of PPI responsiveness. Methods: Twenty-four patients with EoE underwent upper gastrointestinal endoscopy with biopsies from the mid-esophagus for proteomic and Galectin-3 (Gal-3) immunohistochemical analyses. Twenty patients also underwent HRM for IBP assessment. Proteomic profiles were compared between PPI-responsive and non-responsive patients. Results: IBP significantly differed among healthy controls, PPI-responsive, and PPI-non-responsive patients. Proteomic analysis identified 1445 proteins, including 456 shared proteins and 58 differentially expressed proteins among responder groups. Immunohistochemistry demonstrated significantly higher Gal-3 expression in PPI-responsive patients than in non-responders, confirmed by quantitative image analysis (% positive cells, p < 0.01; % positive area, p < 0.005). Conclusions: Integration of HRM with proteomic and immunohistochemical analyses identified functional and molecular differences associated with PPI responsiveness in EoE. Galectin-3 and IBP emerged as candidate biomarkers associated with treatment response. These findings require validation in larger, independent cohorts before their potential clinical utility for patient stratification can be established.