EoE ToT Module 4 References-Wen et al J Allergy Clin Immunol 2015 Transciptome analysis of PPI responsive EoE reveals PPI reversible allergic inflammation

Wen et al J Allergy Clin Immunol 2015 Transciptome analysis of PPI responsive EoE reveals PPI reversible allergic inflammation

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The study examines the molecular characteristics and treatment response of PPI-responsive esophageal eosinophilia (PPI-REE) compared to eosinophilic esophagitis (EoE). While both conditions present similar clinical symptoms and esophageal eosinophilia, EoE is driven by allergic inflammation, whereas the underlying mechanisms of PPI-REE remain unclear. Using esophageal biopsy samples from multiple institutions, the researchers applied an esophageal diagnostic panel (EDP) to analyze gene expression profiles.<br /><br />Key findings include:<br />1. **Molecular Similarity**: The transcriptional profiles of PPI-REE and EoE overlap significantly, involving genes associated with eosinophil chemotaxis, barrier function, tissue remodeling, and mast cells, indicating a shared allergic, Th2-mediated inflammatory pathway.<br />2. **Reversibility with PPI Therapy**: PPI therapy nearly completely reversed the inflammatory gene expression signature in PPI-REE, normalizing it to levels similar to healthy controls. This highlights the anti-inflammatory role of PPIs beyond mere acid suppression.<br />3. **Diagnostic Potential**: Despite the overlap, gene expression analysis identified specific genes, such as KCNJ2, which might help differentiate PPI-REE from EoE before PPI therapy, enabling more targeted treatment strategies.<br />4. **Histological Correlation**: The esophageal eosinophil counts correlated with the molecular EoE scores, reinforcing the genetic heterogeneity observed within PPI-REE cases.<br /><br />This study underscores the distinct, yet molecularly similar nature of PPI-REE and EoE, suggesting that PPI-REE might represent a subtype of EoE. The ability of PPI treatment to reverse the allergic inflammatory signature in PPI-REE provides insight into potential management strategies. Additionally, the identification of differentiating genes, particularly KCNJ2, could lead to earlier and more precise diagnoses, improving patient outcomes and reducing medical costs. The findings prompt a reevaluation of PPI-REE's classification and advocate for further research into its relationship with EoE.

Keywords

PPI-REE

EoE

esophageal eosinophilia

gene expression

PPI therapy

KCNJ2

Th2-mediated inflammation

allergic inflammation

esophageal diagnostic panel

treatment response