Background & Aims: CD8+ T-cell gene expression has been implicated in the pathogenesis of Inflammatory Bowel Diseases (IBD) and has been shown to correlate with disease outcome in adult patients. Moreover, CD8+ T-cell exhaustion was identified as a contributing mechanism that impacts on disease behaviour. We aimed to explore CD8+ T-cell gene expression and DNA methylation in children newly diagnosed with IBD and test their correlation with disease outcome. Methods: We prospectively recruited 112 children with IBD at the point of diagnosis and 19 non-IBD controls. Follow-up samples were obtained from a subset of patients at 3-month intervals (n=62). CD8+ T-cells were purified from peripheral blood samples using magnetic bead sorting and genome-wide transcriptional (n=192) and DNA methylation (n=66) profiles were generated using Affymetrix and Illumina arrays respectively. Publicly available adult CD8+ T-cell transcriptomes and DNA methylomes were included in data analyses to investigate age dependent differences. Results: Variation amongst CD8+ T-cell transcriptomes obtained from children showed association with disease, systemic inflammation, age and gender, but lacked correlation with disease outcome in pediatric IBD. In contrast to CD8+ T-cell transcriptomes in adult Crohn's Disease (CD), samples from pediatric patients did not show variation within genes forming part of the previously reported prognostic expression or T-cell exhaustion signatures. Pediatric CD patient derived DNA methylation profiles also lacked correlation with disease outcome but in comparison to adult CD8+ methylomes showed a higher predicted proportion of CD8+ naïve T-cells. Conclusions: Our findings indicate age-related differences in IBD pathogenesis and highlight the importance of validating adult clinical biomarkers in pediatric cohorts.

CD8+ T-cell transcription and DNA methylation show age specific differences and lack correlation with clinical outcome in pediatric Inflammatory Bowel Disease