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A miRNA-Based Blood and Mucosal Approach for Detecting and Monitoring Celiac Disease

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Abstract

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.

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Acknowledgments

The authors are also grateful to all the patients and subjects who participated in this study and also to Cristian Flores, Amaya Oyarzún, and Marjorie de la Fuente for their valuable contributions to laboratory procedures and measurements. The authors acknowledge BioDiagene®, Palermo, Italy, for supplying the genotyping kits.

Funding

This work was supported by the National Fund for the Development of Science and Technology (FONDECYT, Chile) to FPB [Grant No. 1130240] and Italy’s Ministry of Health and Lombardy’s Regional Government Authority (Ministero della Salute e Regione Lombardia) to LE [Grant No. 2011-02348234].

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Correspondence to Karla A. Bascuñán.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Bascuñán, K.A., Pérez-Bravo, F., Gaudioso, G. et al. A miRNA-Based Blood and Mucosal Approach for Detecting and Monitoring Celiac Disease. Dig Dis Sci 65, 1982–1991 (2020). https://doi.org/10.1007/s10620-019-05966-z

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  • DOI: https://doi.org/10.1007/s10620-019-05966-z

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