Circulating miRNAs as Potential Biomarkers for Celiac Disease Development
Year: 2021
Type: article
Study design: Observational Study
Abstract: Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine. Conclusions: We identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.
Source: Frontiers in Immunology
Authors: Ineke L. Tan, Rodrigo Coutinho de Almeida, Rutger Modderman, Anna Stachurska, Jackie Dekens, Donatella Barisani, Caroline R. Meijer, María Roca, Eva Martinez-Ojinaga, Raanan Shamir, Renata Auricchio, Ilma R. Korponay-Szabó, Gemma Castillejo, Hania Szajewska, Sibylle Koletzko, Alexandra Zhernakova, Vinod Kumar, Yang Li, Marijn C. Visschedijk, Rinse K. Weersma, Riccardo Troncone, M. Luisa Mearin, Cisca Wijmenga, Iris Jonkers, Sebo Withoff
Institutions: University Medical Center Groningen, University of Groningen, Leiden University Medical Center, University of Milano-Bicocca, Hospital Universitari i Politècnic La Fe, Instituto de Investigación Sanitaria La Fe, Tel Aviv University, Schneider Children's Medical Center, University of Naples Federico II, University of Debrecen, Heim Pál Országos Gyermekgyógyászati Intézet, Institut de Recerca Biomèdica Catalunya Sud, Hospital Universitari Sant Joan de Reus, Universitat Rovira i Virgili, Medical University of Warsaw, LMU Klinikum, University of Warmia and Mazury in Olsztyn, Ludwig-Maximilians-Universität München, Radboud University Nijmegen, Radboud University Medical Center, Medizinische Hochschule Hannover, Radboud Institute for Molecular Life Sciences, Helmholtz Centre for Infection Research, Centre for Individualised Infection Medicine, Center for Experimental and Clinical Infection Research
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G1362555634, G1824453215, G2011482319, G205760306, G2861369480, Netherlands Organ-on-Chip Initiative, G2948690197, G3207356259, G3393233468, G3802917934, G393177772, G4053523688, G420050720, G42952139, G434927953, G4496278011, G5220780369, G5702163051, G579486543, G6021632493, Exposome-NL, Small changes, big effects: Finding the regulators of immune-mediated disease, G6295775276, G650969681, G7209015420, G8031923243, G828378399
OpenAlex ID: W4200354934