BackgroundRecently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; 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 (non‐responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways.ResultsComparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder‐PrePPI, non‐responder‐PrePPI, and non‐responder‐PostPPI) and without inflammation (controls and responder‐PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder‐PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder‐PrePPI and non‐responder‐PrePPI EoE patients before treatment.ConclusionThese 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.

中文翻译：

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质子泵抑制剂对嗜酸性食管炎食管蛋白特征的影响、治疗反应的预测和评估


背景最近，我们在嗜酸性食管炎（EoE）患者的食管上皮中发现了一种失调的蛋白质特征，包括与炎症和上皮屏障功能相关的蛋白质；然而，质子泵抑制剂（PPI）治疗对此特征的影响尚不清楚。在此，我们使用蛋白质组学方法来研究：(1) PPI 治疗是否改变了 EoE 患者中观察到的食管上皮蛋白质谱，以及 (2) 基线时的蛋白质特征是否可以预测 PPI 反应。成人 EoE 队列（ n = 25) 患者和健康对照 (C) ( n = 10）。在 EoE 患者中，在 8 周 PPI 治疗之前（前）和之后（后）进行食管活检，以确定组织学反应。 PPI后嗜酸性粒细胞计数用于对患者进行分类：≥15个嗜酸性粒细胞/hpf为无应答者（non-responder），<15个嗜酸性粒细胞/hpf为应答者（R）。确定了蛋白质特征，并对差异积累的蛋白质进行了表征，以识别改变的生物过程和信号通路。结果对组间差异积累的蛋白质进行比较分析，揭示了三组炎症患者（有反应者-PrePPI、无反应者-PrePPI 和无反应者）之间的共同特征。 ‐应答者‐PostPPI）并且没有炎症（对照和应答者‐PostPPI）。 PPI 治疗几乎逆转了 EoE 特异性食管蛋白特征，在 PPI 后反应者中，该蛋白富含与炎症和上皮屏障功能相关的通路。此外，我们还确定了一组候选蛋白，用于在治疗前区分有反应者 PrePPI 和无反应者 PrePPI EoE 患者。结论这些发现提供了PPI治疗逆转EoE特征的食管炎症和上皮蛋白改变的证据，从而为PPI临床反应机制提供了新的见解。有趣的是，我们的结果还表明，可以在 EoE 基线上预测 PPI 反应。