Circulating miRNAs as Potential Biomarkers for Celiac Disease Development

Area of Science:

• Molecular biology and immunology
• Gastroenterology and diagnostics

Background:

• Celiac disease (CeD) is an immune-mediated enteropathy triggered by gluten, affecting approximately 1% of the European population.
• Current diagnostic methods lack predictive biomarkers for CeD development.
• MicroRNAs (miRNAs) are regulators of gene expression, and their profiles can be disease-specific.

Purpose of the Study:

• To investigate the potential of circulating miRNAs as predictive biomarkers for the development of celiac disease.
• To identify specific miRNAs that are deregulated before the onset of clinical symptoms or antibody positivity.

Main Methods:

• Next-generation miRNA sequencing was performed on over 200 serum samples from 53 participants in the PreventCD study.
• Samples were collected longitudinally from 3 months of age, including time points before diagnosis and after starting a gluten-free diet (GFD).
• Validation was conducted using two additional cohorts and analysis of miRNAs in duodenal biopsies.

Main Results:

• 53 circulating miRNAs were found to be differentially expressed in individuals who developed CeD compared to controls.
• Eight specific miRNAs were significantly altered in samples taken less than one year before anti-transglutaminase antibody (TGA) positivity.
• Fifteen biomarker candidates showed concordant expression changes in both circulating samples and duodenal biopsies, suggesting an intestinal origin.

Conclusions:

• Circulating miRNAs represent promising early biomarkers for predicting celiac disease development.
• Several identified miRNAs can be detected more than a year prior to seroconversion (TGA positivity).
• Some deregulated miRNAs show a tendency to normalize following a gluten-free diet, indicating potential for monitoring treatment response.