MicroRNAs in Plasma-Derived Extracellular Vesicles as Non-Invasive Biomarkers for Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory esophageal disorder. The lack of non-invasive biomarkers currently results in dependency on endoscopy with biopsies for its diagnosis and monitoring. We aimed to identify potential non-invasive biomarkers using microRNAs (miRNAs) in plasma-derived extracellular vesicles (pEVs). This was a prospective single-center observational study of a discovery cohort of EoE patients (n = 26) with active disease (EoE.Basal) and after anti-inflammatory treatment (EoE.Post.tx) and control subjects (n = 16). Small-RNA-seq was performed to identify differentially regulated small RNAs (sRNAs). Candidate miRNAs were validated in an independent cohort (EoE patients, n = 33; controls, n = 14). The pEVs-sRNA cargo differed among conditions. Compared with controls, Ser_Comb_22, Leu_Comb_5, miR-10b-5p, and miR-125a-5p were upregulated in EoE.Basal, and miR-224-5p, miR-221-3p, let-7d-5p, and miR-191-5p were downregulated. The combination of miR-221-3p and miR-10b-5p showed the best diagnostic performance. Comparing paired EoE samples, miR-374a-5p and miR-30a-3p were upregulated in EoE.Basal, while miR-15a-5p and let-7d-5p were downregulated. Combined miR-30a-3p and miR-15a-5p showed the best AUC values, and miR-30a-3p alone was best as a monitoring biomarker (p = 0.001). In conclusion, pEVs-sRNA changed upon inflammation in EoE patients, and miR-30a-3p was proposed as a potential biomarker for monitoring the treatment. This study was the first to explore the use of pEVs as a non-invasive biomarker for EoE.