PSMB8 stratifies therapy response in eosinophilic esophagitis

Proton pump inhibitors (PPIs) are an effective first-line treatment for eosinophilic esophagitis (EoE). However, half of the patients are refractory to PPI therapy, and predictive markers for therapy decision are lacking. Thus, this study aimed to investigate the differences in esophageal immunologic transcriptome between PPI-non-responders and PPI-responders and identify molecular biomarkers to guide therapy decisions. Forty-eight pediatric EoE patients were enrolled and classified due to PPI-therapy response. Pre-treatment esophagus biopsy was collected for gene expression analysis, differentially expressed genes (DEGs) between PPI-responders and non-responders were identified, followed by gene enrichment and protein-protein interaction network analyses. Expression of identified hub genes was confirmed by immunohistochemistry in an extended cohort comprising 62 patients. PPI-non-responders and responders exhibit a partially different transcriptomic profile, as 12 DEGs were up-regulated and one down-regulated. These DEGs are closely related to antigen processing and presentation function. PSMB8 was identified as a hub gene differing between these two groups, and immunohistochemistry confirmed significantly increased expression in PPI-non-responders (P < 0.0001). Notably, receiver operating characteristic curves curve analysis of PSMB8 reveals it as highly predictive for PPI response (sensitivity/specificity: 0.61/1.00). PPI-non-responding EoE patients exhibited a more profound dysregulation of gene expression. PSMB8 represents a promising esophageal biomarker for predicting therapy response in pediatric EoE.