P111 Clinical validation of a blood-based prognostic biomarker in Inflammatory bowel disease; towards personalised medicine in IBD
1University of Cambridge, Department of Medicine, Cambridge, UK
The inherent patient to patient variability in disease course observed in inflammatory bowel disease (IBD incorporating both Crohn’s disease and ulcerative colitis) has a direct impact on disease management; patients with aggressive disease are undertreated by conventional ‘step-up’ therapy, whilst those with indolent disease would be exposed to the risks and side-effects of unnecessary immunosuppression if a ‘top-down’ approach was indiscriminately used. We previously described, a transcriptional signature detectable within peripheral blood CD8+ T cells of IBD patients at diagnosis, which correlates with subsequent disease course (McKinney et al.
We simultaneously obtained a whole blood PAXgene RNA tube and peripheral blood CD8+ T-cell sample from a training cohort of 69 newly diagnosed IBD patients, Gene expression in both samples was measured by microarray and machine learning used to identify a transcriptional classifier in whole blood gene expression data that would re-capitulate the CD8+ transcriptional subgroups and correlated with prognosis. The classifier was initially trained using leave-one-out cross-validation, and the genes identified were subsequently tested by qPCR and an optimised qPCR assay developed. Independent validation of the biomarker was established using a second, independent validation cohort of 84 newly diagnosed patients with IBD from 4 sites around the UK.
This validated the biomarker and confirmed that the subgroups it identified had significantly different disease courses (analogous to those observed with the CD8+ T-cell subgroups). We have now extended this data set and embarked on the PROFILE trial: PRedicting Outcomes For Crohn’s dIsease using a moLecular biomarker.
We have developed, optimised and validated a whole blood qPCR classifier that is able to predict disease course from diagnosis in IBD patients. This represents a major step towards personalised therapy in IBD, and is currently being used investigate whether this could make personalised medicine a reality in CD.