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FP7 BIOMARGIN shows that a small set of blood micro-RNAs is associated with acute kidney allografts rejection

Abstract : Background: FP7 Biomargin aimed at detecting and validating biomarkers of kidney graft lesions. In this study, we investigated the diagnostic potential of microRNAs (miRNAs) in whole blood samples. Methods/Materials: Blood samples were collected at the time of protocol or for-cause biopsies in 4 European clinical centers. Biopsies were retrospectively selected after centralized histological reading by expert pathologists, and classified into 4 groups (Normal, ABMR, TCMR or IF/TA), to build two independent case-control studies (discovery- and selection sets). Global microRNA (miRNAs) profiling was performed on blood samples from the discovery set by microfluidic cards. A statistical pipeline including 2 uni- and 5 multivariate analyses was applied to identify a list of biomarker candidates associated with one of the 4 groups. This list of miRNAs was quantified using custom TLDA plates on the selection set. Multivariate models were then built to define miRNAs signature of graft lesions. Results: A total of 754 miRNAs was quantified in the discovery set that included 42 Normal, 17 TCMR, 37 IF/TA and 30 ABMR samples. Our statistical pipeline identified 141 candidates that were assessed in the selection cohort of 37 Normal, 23 TCMR, 41 IF/TA and 37 ABMR samples. The table shows the association between histological phenotypes and miR-derived statistical models in the selection cohort. Conclusion: We identified a small subset of miRNAs in the blood with a strong association with ABMR and/or TCMR, thus providing the basis for innovative non-invasive molecular tools development. Their diagnostic performance is currently being investigated in blood samples collected at time of 453 consecutive allograft biopsies in our BIOMARGIN trans-sectional study.
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Submitted on : Friday, September 28, 2018 - 12:35:12 PM
Last modification on : Sunday, June 26, 2022 - 1:21:59 PM

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Claire Tinel, A. Benon, Stéphane Gazut, Maarten Naesens, Wilfried Gwinner, et al.. FP7 BIOMARGIN shows that a small set of blood micro-RNAs is associated with acute kidney allografts rejection. 17th Annual Congress of the French Speaking Society of Transplantation, Société Francophone de Transplantation, Dec 2017, Poitiers - La Rochelle, France. p5 - O4, ⟨10.1111/tri.13101⟩. ⟨cea-01883568⟩



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