OP34 Whole blood profiling of T-cell-derived miRNA allows the development of prognostic models in inflammatory bowel disease
R. Kalla1, A. Adams2, R. White3, C. Clarke4, A. Ivens3, N. Ventham5, N. Kennedy6, S. McTaggart7, I. IBD Character Consortium8, G.T. Ho1, A. Buck3, J. Satsangi2, IBD Character Consortium
1Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK, 2Nuffield Department of Medicine, University of Oxford, Oxford, UK, 3School of Biological Sciences, University of Edinburgh, Edinburgh, UK, 4LifeArc, Edinburgh BioQuarter, Edinburgh, UK, 5Centre for Genomics Medicine, University of Edinburgh, Edinburgh, UK, 6Department of Gastroenterology, University of Exeter, Exeter, UK, 7Norwich Research Centre, Earlham Institute, Norwich, UK, 8European Commission, Research and Innovation, Brussels, Belgium
Background
There is an unmet need for blood-based biomarkers that help predict disease and its course at inception to allow tailoring of treatments, achieve early mucosal healing and improve clinical outcomes. In our study, we explore the clinical utility of miRNAs in Inflammatory bowel disease (IBD).
Methods
A 2-stage prospective multi-centre case–control study was performed. Small RNA sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes (90 CD4+ and CD8+ T-lymphocytes and CD14+ monocytes) from 32 patients (9 CD, 14 UC, 8 healthy controls) to identify differentially expressed cell-specific miRNAs.Top miRNAs were then validated in whole blood in 294 treatment naïve newly diagnosed IBD and non-IBD patients (97 UC, 98 CD, 98 non-IBD) using RT-qPCR, recruited across 5 centres in UK and Europe. Phenotype and outcome data were collected and Cox proportional hazards were derived to assess the contribution of each miRNA to outcomes; defined as the need for 2 or more immunosuppressants and/or surgery after initial disease remission. RT-qPCR target miRNA relative quantification was calculated using 2−ΔΔCq method.
Results
Each leucocyte subset (30 CD4+ T cells, 28 CD8+ T cells and 32 CD14+ monocytes) was analysed between disease and controls, adjusting for age, gender and batch effects. A total of three miRNAs differentiated IBD from controls in CD4+ T cells including miR-1307-3p (FDR
Conclusion
We have identified unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These blood-based miRNAs are able to predict treatment escalation at disease inception and have the potential for clinical translation.