Author, as appears in the article.: Tan IL; Coutinho de Almeida R; Modderman R; Stachurska A; Dekens J; Barisani D; Meijer CR; Roca M; Martinez-Ojinaga E; Shamir R; Auricchio R; Korponay-Szabó IR; Castillejo G; Szajewska H; Koletzko S; Zhernakova A; Kumar V; Li Y; Visschedijk MC; Weersma RK; Troncone R; Mearin ML; Wijmenga C; Jonkers I; Withoff S
Department: Medicina i Cirurgia
URV's Author/s: Castillejo De Villasante, Gemma
Keywords: Small rna sequencing Pre-diagnostic marker Pre-clinical marker Diagnosis Celiac disease Autoimmunity society profiles pre-diagnostic marker pre-clinical marker microrna management il-15 guidelines expression disorders celiac disease cancer autoimmunity
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: 53 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 <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. Copyright © 2021 Tan, Coutinho de Almeida, Modderman, Stachurska, Dekens, Barisani, Meijer, Roca, Martinez-Ojinaga, Shamir, Auricchio, Korponay-Szabó, Castillejo, Szajewska, Koletzko, Zhernakova, Kumar, Li, Visschedijk, Weersma, Troncone, Mearin, Wijmenga, Jonkers and Withoff.
Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Odontología Nutrição Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Immunology and allergy Immunology Farmacia Engenharias iii Engenharias ii Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciência de alimentos Biotecnología Biodiversidade
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: gemma.castillejo@urv.cat
Record's date: 2024-07-27
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.frontiersin.org/articles/10.3389/fimmu.2021.734763/full
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Frontiers In Immunology. 12
APA: Tan IL; Coutinho de Almeida R; Modderman R; Stachurska A; Dekens J; Barisani D; Meijer CR; Roca M; Martinez-Ojinaga E; Shamir R; Auricchio R; Korponay (2021). Circulating miRNAs as Potential Biomarkers for Celiac Disease Development. Frontiers In Immunology, 12(), -. DOI: 10.3389/fimmu.2021.734763
Article's DOI: 10.3389/fimmu.2021.734763
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV