Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.

Autor: Kalla, R, Adams, A T, Ventham, N T, Kennedy, N A, White, R, Clarke, C, Ivens, A, Bergemalm, D, Vatn, S, Lopez-Jimena, B, Consortium, IBD Character, Ricanek, P, Vatn, M H, Söderholm, Johan D, Gomollón, F, Nowak, J K, Jahnsen, J, Halfvarson, J, McTaggart, S, Ho, G T
Zdroj: Journal of Crohn's & Colitis; Dec2020, Vol. 14 Issue 12, p1724-1733, 10p
Abstrakt: Background MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. Methods In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn's disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. Results In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [ p  = 0.01], miR-3615 [ p  = 0.02] and miR-4792 [ p  = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20–3.27; logrank p  = 1.80 × 10–3), in particular CD [HR 2.81; IQR: 1.11–3.53, p  = 6.50 × 10–4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. Interpretation We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated. [ABSTRACT FROM AUTHOR]
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