Salivary Microrna As a Biomarker for Monitoring Response to Treatment in Eosinophilic Esophagitis

Abstract

RationaleEosinophilic esophagitis (EoE) is a clinicopathological condition where endoscopic biopsies of the esophagus are required for diagnosis and monitoring the response to treatment. No non-invasive method of monitoring currently exists. MicroRNA (miRNA), regulate expression of many cytokines important in allergic disease and have been found in saliva. We hypothesize that salivary miRNAs are differentially expressed in EoE and can be used as biomarkers to monitor the response to treatment.MethodsAfter IRB approval, fifteen adult patients with EoE (symptoms consistent with EoE, endoscopic biopsy with ≥15 eosinophils per high powered field, and previous proton pump inhibitor therapy) were randomly enrolled to provide a saliva sample before and after 2 months of swallowed fluticasone therapy. Differences of miRNA expression were compared to healthy controls (n=17) using Wilcoxin rank sum testing. Expression changes before and after treatment were analyzed by paired T-test. A significance cutoff of <0.05 was used for all analyses.ResultsAll but two patients had complete resolution of their symptoms on swallowed fluticasone. MiRNA expression profiles comparing EoE patients and healthy controls demonstrated > 2-fold up-regulation of miR-570-3p, -3613-5p, -4668-5p, and -30a-5p in EoE (p<0.01). After treatment, expression of miR-658 increased while expression of miR-3613-5p and -4668-5p decreased (p= 0.0027, 0.0314, and 0.0488 respectively). These results suggest miRNA expression differences can be seen at time of diagnosis and can change with treatment of EoE.ConclusionsSalivary miRNA represents a promising new tool for non-invasive, biomarker monitoring of EoE. These differentially expressed miRNAs may have pathogenic roles in EoE. RationaleEosinophilic esophagitis (EoE) is a clinicopathological condition where endoscopic biopsies of the esophagus are required for diagnosis and monitoring the response to treatment. No non-invasive method of monitoring currently exists. MicroRNA (miRNA), regulate expression of many cytokines important in allergic disease and have been found in saliva. We hypothesize that salivary miRNAs are differentially expressed in EoE and can be used as biomarkers to monitor the response to treatment. Eosinophilic esophagitis (EoE) is a clinicopathological condition where endoscopic biopsies of the esophagus are required for diagnosis and monitoring the response to treatment. No non-invasive method of monitoring currently exists. MicroRNA (miRNA), regulate expression of many cytokines important in allergic disease and have been found in saliva. We hypothesize that salivary miRNAs are differentially expressed in EoE and can be used as biomarkers to monitor the response to treatment. MethodsAfter IRB approval, fifteen adult patients with EoE (symptoms consistent with EoE, endoscopic biopsy with ≥15 eosinophils per high powered field, and previous proton pump inhibitor therapy) were randomly enrolled to provide a saliva sample before and after 2 months of swallowed fluticasone therapy. Differences of miRNA expression were compared to healthy controls (n=17) using Wilcoxin rank sum testing. Expression changes before and after treatment were analyzed by paired T-test. A significance cutoff of <0.05 was used for all analyses. After IRB approval, fifteen adult patients with EoE (symptoms consistent with EoE, endoscopic biopsy with ≥15 eosinophils per high powered field, and previous proton pump inhibitor therapy) were randomly enrolled to provide a saliva sample before and after 2 months of swallowed fluticasone therapy. Differences of miRNA expression were compared to healthy controls (n=17) using Wilcoxin rank sum testing. Expression changes before and after treatment were analyzed by paired T-test. A significance cutoff of <0.05 was used for all analyses. ResultsAll but two patients had complete resolution of their symptoms on swallowed fluticasone. MiRNA expression profiles comparing EoE patients and healthy controls demonstrated > 2-fold up-regulation of miR-570-3p, -3613-5p, -4668-5p, and -30a-5p in EoE (p<0.01). After treatment, expression of miR-658 increased while expression of miR-3613-5p and -4668-5p decreased (p= 0.0027, 0.0314, and 0.0488 respectively). These results suggest miRNA expression differences can be seen at time of diagnosis and can change with treatment of EoE. All but two patients had complete resolution of their symptoms on swallowed fluticasone. MiRNA expression profiles comparing EoE patients and healthy controls demonstrated > 2-fold up-regulation of miR-570-3p, -3613-5p, -4668-5p, and -30a-5p in EoE (p<0.01). After treatment, expression of miR-658 increased while expression of miR-3613-5p and -4668-5p decreased (p= 0.0027, 0.0314, and 0.0488 respectively). These results suggest miRNA expression differences can be seen at time of diagnosis and can change with treatment of EoE. ConclusionsSalivary miRNA represents a promising new tool for non-invasive, biomarker monitoring of EoE. These differentially expressed miRNAs may have pathogenic roles in EoE. Salivary miRNA represents a promising new tool for non-invasive, biomarker monitoring of EoE. These differentially expressed miRNAs may have pathogenic roles in EoE.