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

Abstract

Eosinophilic esophagitis (EoE) is a chronic, Th2-inflammatory disease of the esophagus that can severely affect food intake. Currently, diagnosis and assessing response to treatment of EoE is highly invasive and requires endoscopy with esophageal biopsies. Finding non-invasive and accurate biomarkers is important for improving patient well-being. Unfortunately, EoE is usually accompanied by other atopies, which make it difficult to identify specific biomarkers. Providing an update of circulating EoE biomarkers and concomitant atopies is therefore timely. This review summarizes the current knowledge in EoE blood biomarkers and two of its most common comorbidities, bronchial asthma (BA) and atopic dermatitis (AD), focusing on dysregulated proteins, metabolites, and RNAs. It also revises the current knowledge on extracellular vesicles (EVs) as non-invasive biomarkers for BA and AD, and concludes with the potential use of EVs as biomarkers in EoE.

Identification of CXC Chemokine Receptor 2 (CXCR2) as a Novel Eosinophils-Independent Diagnostic Biomarker of Pediatric Eosinophilic Esophagitis by Integrated Bioinformatic and Machine-Learning Analysis

“… 69 As to the microbial components of esophageal mucosa, healthy flora mainly consisted of: Streptococci , while flora in EoE enriched Neisseria, Corynebacterium , and Haemophilus , and downregulated Porphyromonas . 67 Furthermore, former attempts testing fractionated exhaled nitric oxide testing (FeNO) and salivary miRNA levels (miR-26b-5p, miR-27b-3p, Let-7i-5p, miR-142-5p, miR-30a-5p, and miR-205-5p), performed not well in differentiating EoE and healthy samples, 70 , 71 with the alliance of the above-mentioned six miRNAs reached a 70% sensitivity and 68% specificity in children despite that miR-205-5p had the largest difference between the EoE and non-EoE groups. 71 Other works determined some candidate salivary miRNAs in adults, such as miR-4668-5p, while their efficacy in pediatric samples required evaluation.…”

Extracellular vesicles: Messengers of allergic immune responses and novel therapeutic strategy

“…Because of their decisive role in intercellular communication, EVs are not only interesting for their involvement in the pathogenesis of allergic diseases but also for their possible applications in diagnostic or therapeutic settings. EVs are considered promising biomarkers due to their abundance in all body fluids, resemblance to parental cells, and cargo stability [2, 33] (Fig. 2B).…”

Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics

“…In terms of histological remission [ 56 ], EoE symptoms have repeatedly been shown not to be reliable enough to be used to monitor treatment response; for PPI therapy, clinical remission rates repeatedly exceed those of histological remission. Despite considerable effort to identify non- or minimally invasive methods to assess esophageal inflammation in EoE [ 57 ], endoscopy with biopsies currently remains the only accurate procedure. Therefore, a follow-up assessment based on endoscopy with biopsies should be performed 8–12 weeks after the initiation of any induction treatment based on PPIs for active EoE, or after any major treatment change (e.g., dose reduction or withdrawal of maintenance therapy) [ 58 ].…”