11/12/2025
Study Reveals Key Molecular Differences Between PPI-Responsive and PPI-Unresponsive Eosinophilic Esophagitis
New research from our team reveals that pediatric patients with eosinophilic esophagitis (EoE) have distinct molecular signatures that may predict treatment response to proton pump inhibitors (PPIs).
Through comprehensive RNA-sequencing of esophageal biopsies, we discovered that while PPI-responsive (PPI-R) and PPI-unresponsive (PPI-UR) EoE patients appear clinically identical at diagnosis, they exhibit unique transcriptional profiles. PPI-R EoE shows enrichment in interferon signaling and zinc ion regulation pathways, whereas PPI-UR EoE displays heightened type 2 inflammation, enhanced B cell and neutrophil signatures, and—most notably—a sustained esophageal epithelial proliferative response driven by cell cycle and division genes.
Importantly, we identified a proinflammatory SFRP1+ esophageal suprabasal cell population that persists in PPI-UR EoE even after treatment, suggesting a STAT3-dependent mechanism that may explain PPI resistance.
These findings represent a crucial step toward precision medicine in EoE management, identifying potential biomarkers that could guide initial therapy selection and prevent disease progression during ineffective treatment periods.
Read the full study in JCI Insight: https://doi.org/10.1172/jci.insight.178595
