S497 Effect of Proton Pump Inhibitor Treatment in “PPI Non-Responsive” Patients With Eosinophilic Esophagitis

Thakkar, Kisan; Philpott, Hamish; LaFata, Sean; Fowler, Mark R.; Keene, Staci; Iuga, Alina; Dellon, Evan S.

doi:10.14309/01.ajg.0000858628.27655.a4

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“…It has been previously reported that some EoE patients have a decline in eosinophil count after PPI treatment without achieving histologic response, whereas in other cases histologic parameters such as lamina propria fibrosis, eosinophil degranulation, and basal cell hyperplasia also decrease 26–28 . Interestingly, although no DAP were found between NR-PrePPi and NR-Post PPI (Figure 2 and supplementary File1-Table 7), a partial recovery of the protein signature was also observed in non-responder patients (Figure 1).…”

Section: Discussionmentioning

confidence: 98%

Proton pump Inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction and evaluation of treatment response

Molina-Jiménez,

Ugalde-Triviño,

Arias-González

et al. 2023

Preprint

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BackgroundRecently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. 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.MethodsWe evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n=25) patients and healthy controls (C) (n=10). In EoE patients, esophageal biopsies were taken before (Pre) and after (Post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (NR) and <15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins (DAP) were characterized to identify altered biological processes and signaling pathways.ResultsHigh dimensional analysis of DAP between groups revealed common signatures between three groups of patients with inflammation (R-PrePPI, NR-PrePPI and NR-PostPPI) and without inflammation (C and R- PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in R-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate R-PrePPI and NR-PrePPI EoE patients before treatment.ConclusionThese findings provide evidence that PPI therapy reverses the alterations in the protein profile associated with EoE. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

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Section: Discussionmentioning

confidence: 98%