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A miRNA-Based Blood and Mucosal Approach for Detecting and Monitoring Celiac Disease
Karla A Bascuñán1,2, Francisco Pérez-Bravo3,4, Gabriella Gaudioso5
1Department of Nutrition, School of Medicine, University of Chile, Av. Independencia 1027, Independencia, 8380453, Santiago, Chile. kbascunan@med.uchile.cl.
Background:
The role of microRNAs (miRNAs) in celiac disease (CD) is unclear.
Aims:
We evaluated inflammation-related miRNA-146a, miRNA-155, miRNA-21, and miRNA-125b expression in peripheral blood and intestinal mucosa of CD adults.
Methods:
Thirty patients with CD were included: patients with active CD on a gluten-containing diet (CD-active, n = 10), patients on a gluten-free diet (for at least 1 year), and patients with negative blood antibodies (CD-inactivePE, n = 10). In addition, ten healthy volunteers formed the comparison/control group. MiRNA expression was measured in duodenal biopsies from patients (CD-inactiveMU, n = 10) after in vitro exposure to PT gliadin and 33-mer peptide. MiRNAs expression was measured in plasma and in peripheral blood mononuclear cells (PBMCs) and monocytes, before and after in vitro exposure to native gliadin (gliadinN).
Results:
Expression levels of miRNA-146a, miRNA-155, and miRNA-21 in PBMCs, miRNA-155 in monocytes and miRNA-155, miRNA-21, and miRNA-125b in plasma were elevated in both groups of celiac patients. After in vitro exposure with gliadinN, miRNA-146a and miRNA-155 expression markedly increased in PBMCs and monocytes, while miRNA-155 and miRNA-21 increased in the CD-active group. MiRNAs expression in intestinal mucosa did not change. MiRNA-146a and miRNA-155 expression showed high sensitivity and specificity for the presence of CD, irrespective of the current dietary treatment.
Conclusions:
Selected inflammation-related miRNAs expression is elevated in the peripheral blood of celiac. This suggests their participation in the immune processes underlying the pathology. Their similar response in active and inactive CD suggests that they should be further evaluated, as potential diagnostic biomarkers for CD.
Insights
Inflammation-related microRNAs (miRNAs) are elevated in the blood of individuals with celiac disease (CD). These miRNAs show potential as diagnostic biomarkers for CD, regardless of diet.
Area of Science:
- Immunology
- Molecular Biology
- Gastroenterology
Background:
- The precise role of microRNAs (miRNAs) in the pathogenesis of celiac disease (CD) remains incompletely understood.
- Investigating specific miRNAs involved in inflammation is crucial for understanding CD.
- Celiac disease is an autoimmune disorder triggered by gluten ingestion.
Purpose of the Study:
- To evaluate the expression of inflammation-related miRNAs (miRNA-146a, miRNA-155, miRNA-21, and miRNA-125b) in the peripheral blood and intestinal mucosa of adult celiac disease patients.
- To assess the changes in miRNA expression following in vitro gluten exposure.
- To determine the potential of these miRNAs as diagnostic biomarkers for celiac disease.
Main Methods:
- Studied 30 adult celiac disease patients (active CD, inactive CD on gluten-free diet, and CD with negative antibodies) and 10 healthy controls.
- Measured miRNA expression in plasma, peripheral blood mononuclear cells (PBMCs), and monocytes.
- Analyzed miRNA expression in duodenal biopsies before and after in vitro exposure to gliadin peptides.
Main Results:
- Elevated levels of miRNA-146a, miRNA-155, and miRNA-21 were observed in PBMCs, and miRNA-155, miRNA-21, and miRNA-125b in plasma of celiac patients.
- In vitro gliadin exposure significantly increased miRNA-146a and miRNA-155 expression in PBMCs and monocytes.
- Intestinal miRNA expression did not significantly change, but miRNA-146a and miRNA-155 demonstrated high sensitivity and specificity for CD detection.
Conclusions:
- Selected inflammation-related miRNAs are upregulated in the peripheral blood of individuals with celiac disease.
- These miRNAs are implicated in the immune response underlying celiac disease pathology.
- The consistent miRNA expression patterns in both active and inactive CD suggest their potential as reliable diagnostic biomarkers for celiac disease.
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