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. 2020 Dec 2;14(12):1724-1733.
doi: 10.1093/ecco-jcc/jjaa134.

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

R Kalla  1 , A T Adams  2 , N T Ventham  3 , N A Kennedy  4 , R White  5 , C Clarke  6 , A Ivens  5 , D Bergemalm  7 , S Vatn  8 , B Lopez-Jimena  6 ; IBD Character Consortium; P Ricanek  8   9 , M H Vatn  9 , Johan D Söderholm  10 , F Gomollón  11 , J K Nowak  2   12 , J Jahnsen  8   9 , J Halfvarson  7 , S McTaggart  6 , G T Ho  1 , A Buck  5 , J Satsangi  2   3
Affiliations
Free article

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

R Kalla et al. J Crohns Colitis. .
Free article

Abstract

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.

Keywords: MicroRNA; T-cell; biomarkers; crohn’s disease; epigenetics; inflammatory bowel disease; mRNA; prognosis; proteins; ulcerative colitis; whole blood.

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