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Whole blood profiling of T-cell derived miRNA allows the development of prognostic models in inflammatory bowel disease

Research output: Contribution to journalArticle

  • A. T. Adams
  • N. A. Kennedy
  • Ruby White
  • C. Clarke
  • D Bergemalm
  • S Vatn
  • B Lopez-jimena
  • P Ricanek
  • Morten H. Vatn
  • Johan D Söderholm
  • F Gomollón
  • J F Nowak
  • Jorgen Jahnsen
  • Jonas Halfvarson

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Original languageEnglish
Article numberjjaa134
JournalJournal of Crohn's and Colitis
Volume14
Issue number6
Early online date29 Jun 2020
DOIs
Publication statusE-pub ahead of print - 29 Jun 2020

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. In our study, we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD.

Methods
In a 2-stage prospective multi-centre case control study, Next Generation sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes from 32 patients (9 CD, 14 UC, 8 healthy controls) and differentially expressed signals were validated in whole blood in 294 patients (97 UC, 98 CD, 98 non-IBD) 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 leucocyte 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 (HR 1.98, 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 2 or more criteria were met and 90% for UC if 3 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.

    Research areas

  • MicroRNA, T-cell, inflammatory bowel disease, crohn’s disease, ulcerative colitis, biomarkers, proteins, prognosis, whole blood, mRNA, epigenetics

ID: 156251832