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001-es BibID:BIBFORM100413
035-os BibID:(cikkazonosító)734763 (WoS)000735534800001 (Scopus)85121575135
Első szerző:Tan, Ineke L.
Cím:Circulating miRNAs as Potential Biomarkers for Celiac Disease Development / Tan Ineke L., Coutinho de Almeida Rodrigo, Modderman Rutger, Stachurska Anna, Dekens Jackie, Barisani Donatella, Meijer Caroline R., Roca María, Martinez-Ojinaga Eva, Shamir Raanan, Auricchio Renata, Korponay-Szabó Ilma R., Castillejo Gemma, Szajewska Hania, Koletzko Sibylle, Zhernakova Alexandra, Kumar Vinod, Li Yang, Visschedijk Marijn C., Weersma Rinse K., Troncone Riccardo, Mearin M. Luisa, Wijmenga Cisca, Jonkers Iris, Withoff Sebo
Dátum:2021
ISSN:1664-3224
Megjegyzések: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.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
mall RNA sequencing
pre-diagnostic marker
pre-clinical marker
autoimmunity
celiac disease
Megjelenés:Frontiers in Immunology. - 12 (2021), p. 1-16. -
További szerzők:Coutinho de Almeida, Rodrigo Modderman, Rutger Stachurska, Anna Dekens, Jackie Barisani, Donatella Meijer, Caroline R. Roca, María Martinez-Ojinaga, Eva Shamir, Raanan (gyermekgyógyász) Auricchio, Renata Korponay-Szabó Ilma (1959-) (gyermekgyógyász) Castillejo, Gemma (gyermekgyógyász, gasztroenterológus) Szajewska, Hania (gyermekgyógyász) Koletzko, Sibylle Zhernakova, Alexandra Kumar, Vinod Li, Yang Visschedijk, Marijn C. Weersma, Rinse K. Troncone, Riccardo Mearin, Maria Luisa Wijmenga, Cisca Jonkers, Iris Withoff, Sebo
Pályázati támogatás:NKFI 120392
OTKA
GINOP-2.3.2-15-2016-00015
GINOP
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