Transcription profiling of CD8 T-cells predicts disease course in Crohn's disease and ulcerative colitis

ABSTRACT: The natural history of Crohn's disease (CD) and ulcerative colitis (UC) is variable. In patients with frequently-relapsing/steroid-refractory disease, sustained remission is more likely if immunomodulators are introduced earlier. However, many patients experience quiescent disease without immunomodulators, and should not be unnecessarily immunosuppressed. Previous attempts to stratify treatment from diagnosis have failed because disease course cannot be reliably predicted. We performed whole genome expression analysis of peripheral CD8 and CD4 T-cells isolated from patients with active, untreated CD or UC. Patients were prospectively managed by clinicians blinded to the microarray results. Analysis of CD8 T-cell gene-expression data revealed two distinct subgroups within each disease cohort, which did not correlate with any contemporaneous laboratory or clinical data. There was considerable overlap in the genes that were differentially expressed between the subgroups in each disease. Patients belonging to one of the subgroups (termed IBD1) experienced significantly more aggressive disease than those in the other (termed IBD2) in both diseases. This was characterised by a greater need to escalate treatment with immunomodulators or surgery in response to relapsing or chronically active disease. Furthermore, this subgroup more frequently required additional interventions due to the initial escalation failing to maintain disease remission. Similar association with disease behaviour could not be demonstrated with CD4 T-cell gene-expression analysis, nor with previously described methods of predicting outcome. Our findings demonstrate that gene-expression profiling of CD8 T-cells at diagnosis can stratify patients with CD or UC according to subsequent disease behaviour and represents a significant step towards personalised therapy.

ORGANISM(S): Homo sapiens

DISEASE(S): Ulcerative colitis

SUBMITTER: Tim Rayner 

PROVIDER: E-MTAB-331 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress