1. Circulating miRNAs as Potential Biomarkers for Celiac Disease Development
- Author
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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, and Sebo Withoff
- Subjects
small RNA sequencing ,pre-diagnostic marker ,pre-clinical marker ,autoimmunity ,celiac disease ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background & AimsCeliac 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.MethodsUsing 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.Results53 circulating miRNAs were increased (27) or decreased (26) in CeD versus 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
- Published
- 2021
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