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Author Spotlight: Investigating the Pathophysiology of Eosinophilic Esophagitis
Published on: May 10, 2024
MiR-21-5p and miR-223-3p as Treatment Response Biomarkers in Pediatric Eosinophilic Esophagitis
Antonietta Tarallo1, Marianna Casertano1, Anna Valanzano1
1Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy.
Insights
Plasma microRNAs miR-21-5p and miR-223-3p show promise as non-invasive biomarkers for pediatric eosinophilic esophagitis (EoE). Their levels decrease with treatment, potentially reducing the need for invasive diagnostic procedures.
Area of Science:
- Gastroenterology
- Molecular Biology
- Pediatric Pathology
Background:
- Eosinophilic esophagitis (EoE) is a common pediatric condition.
- Diagnosis and monitoring often require invasive endoscopy and biopsies.
- There is a need for non-invasive biomarkers to assess disease activity and treatment response.
Purpose of the Study:
- To evaluate plasma levels of miR-21-5p and miR-223-3p as potential non-invasive biomarkers in pediatric EoE.
- To assess the correlation of these microRNAs with disease activity and response to therapy.
- To identify target genes and pathways involved in EoE pathophysiology.
Main Methods:
- Collected plasma and esophageal mucosa samples from 13 pediatric EoE patients and 8 controls at diagnosis and after treatment.
- Analyzed microRNA (miRNA) levels (miR-21-5p, miR-223-3p) and their target genes using extraction and bioinformatic analysis.
- Compared miRNA levels between EoE patients and controls, and before and after therapy.
Main Results:
- Plasma levels of miR-21-5p and miR-223-3p were significantly elevated in pediatric EoE patients compared to controls.
- These miRNA levels in plasma mirrored those in esophageal mucosa.
- Target genes of these miRNAs are involved in key signaling pathways (MAPK, Ras, FoxO) relevant to EoE.
- STAT3 and PTEN, downregulated in EoE mucosa, are implicated in related conditions.
- Following therapy, plasma and tissue miRNA levels significantly decreased, returning to control levels.
Conclusions:
- miR-21-5p and miR-223-3p show potential as complementary non-invasive biomarkers for pediatric EoE.
- These biomarkers may help reduce the reliance on endoscopy and biopsies for diagnosis and monitoring.
- Further research can validate these miRNAs for clinical application in EoE management.
Abstract:
The diagnosis and monitoring of eosinophilic esophagitis (EoE), a common pediatric pathology, typically involves invasive procedures such as an upper endoscopy with biopsies, imposing a significant burden on patients and healthcare systems. We aimed to assess miR-21-5p and miR-223-3p levels in pediatric EoE patients and evaluate their as potential non-invasive biomarkers of disease activity and response to treatments. We enrolled 13 children with EoE and 8 controls. Plasma and esophageal mucosa samples from patients were collected at diagnosis and after 8-10 weeks of therapy and compared with control samples. After microRNA(miRNA) extraction, the levels of miR-21-5p and miR-223-3p and their relevant target genes were analyzed. Bioinformatic analysis was used to identify the predicted target genes and pathways that are potentially relevant for disease pathophysiology. Plasma levels of miR-21-5p and miR-223-3p were significantly higher in EoE patients than in the controls, reflecting their levels in esophageal mucosa. The target genes of these miRNAs are involved in key signaling pathways (MAPK, Ras, and FoxO), relevant for EoE pathophysiology. Among these, STAT3 (Signal Transducer and Activator of Transcription 3) and PTEN (Phosphatase and Tensin Homolog), which are significantly downregulated in patient esophageal mucosa, are implicated in eosinophilic gastroenteropathies and autoimmune diseases. Following therapy (proton pump inhibitors and/or fluticasone propionate), plasma and tissue expression of both miRNAs significantly decreased and were no longer different from the controls. These microRNAs may serve as complementary non-invasive EoE markers and reduce the need for endoscopy/biopsies.
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