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Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (<jats:italic>n<\/jats:italic>\u2009=\u200925) patients and healthy controls (C) (<jats:italic>n<\/jats:italic>\u2009=\u200910). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8\u2010week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: \u226515 eosinophils\/hpf as non\u2010responders (non\u2010responder) and\u2009&lt;\u200915 eosinophils\/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder\u2010PrePPI, non\u2010responder\u2010PrePPI, and non\u2010responder\u2010PostPPI) and without inflammation (controls and responder\u2010PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder\u2010PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder\u2010PrePPI and non\u2010responder\u2010PrePPI EoE patients before treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16261","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T09:41:50Z","timestamp":1722591710000},"page":"3448-3463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4912-1025","authenticated-orcid":false,"given":"Francisca","family":"Molina\u2010Jim\u00e9nez","sequence":"first","affiliation":[{"name":"Molecular Biology Unit Hospital Universitario de la Princesa  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de La Princesa (IIS\u2010IP)  Madrid 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