Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis

Abstract

Objectives: Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton-pump inhibitors (PPI) induce disease remission but no predictive factors of PPI-responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI-R) and nonresponder patients (PPI-NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy. Methods: This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI-R or PPI-NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum. Results: We found several esophageal miRNAs with different expression values between PPI-R and PPI-NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI-R displayed a significant decrease in eotaxin-3, IL-5, IL-13, periostin, and major basic protein ( P < 0.05) and a significant increase in filaggrin levels after PPI treatment ( P < 0.01). Conclusions: Esophageal miRNA levels found are able to discriminate between both PPI-R and PPI-NR at baseline, and before and after treatment in PPI-R, so they could be used as biomarkers. Furthermore, we observed clinical and esophageal molecular restoration in PPI-R patients after PPI therapy.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN

“…We can hypothesize that PPI-responsive patients have an epithelial barrier dysfunction possibly mediated by estrogen-responsive genes, thus making males more prevalent in this group. Further studies analyzing the different molecular expression profiles of PPI responders and non-responders may help to further elucidate these clinical observations (40,41).…”

Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions

“… 127 In a separate study, Cañas et al have identified several microRNAs in esophageal biopsy tissue that may discriminate between PPI responders and non-responders at baseline. 207 …”

Blood-Based Biomarkers for Eosinophilic Esophagitis and Concomitant Atopic Diseases: A Look into the Potential of Extracellular Vesicles

“…Likewise, significant upregulation of serum miR-21 30-fold in EoE correlated with an increased expression 40-fold in the esophageal tissue [ 19 ]. Unfortunately, there is still little evidence of circulating microRNAs in EoE, and other authors failed when they tried to detect them in the serum [ 168 ]. Differences in mRNAs have also been explored as potential circulating biomarkers for EoE [ 169 , 170 , 171 ].…”