PSMB8 stratifies therapy response in eosinophilic esophagitis.

Area of Science:

• Immunology
• Genetics
• Gastroenterology

Background:

• Proton pump inhibitors (PPIs) are a first-line treatment for eosinophilic esophagitis (EoE).
• Approximately 50% of EoE patients exhibit refractoriness to PPI therapy.
• Predictive markers for guiding PPI therapy decisions in EoE are currently lacking.

Purpose of the Study:

• To investigate differences in the esophageal immunologic transcriptome between PPI-responsive and PPI-refractory pediatric EoE patients.
• To identify molecular biomarkers that can predict treatment response to PPIs in EoE.
• To guide personalized therapy decisions for EoE management.

Main Methods:

• Gene expression analysis of pre-treatment esophageal biopsies from 48 pediatric EoE patients.
• Identification of differentially expressed genes (DEGs) between PPI-responders and non-responders.
• Gene enrichment, protein-protein interaction network analyses, and immunohistochemistry confirmation in an extended cohort of 62 patients.

Main Results:

• A distinct transcriptomic profile was observed between PPI-non-responders and responders, with 12 DEGs up-regulated and 1 down-regulated.
• DEGs were primarily associated with antigen processing and presentation pathways.
• PSMB8 was identified as a key hub gene with significantly increased expression in PPI-non-responders, demonstrating high predictive value (sensitivity/specificity: 0.61/1.00).

Conclusions:

• PPI-non-responding EoE patients display more profound gene expression dysregulation.
• PSMB8 is a promising esophageal biomarker for predicting PPI therapy response in pediatric EoE.
• Identifying biomarkers like PSMB8 can facilitate personalized treatment strategies for EoE.