TY - JOUR T1 - CD8<sup>+</sup> T-cell transcription and DNA methylation show age specific differences and lack correlation with clinical outcome in pediatric Inflammatory Bowel Disease JF - bioRxiv DO - 10.1101/2020.03.30.015446 SP - 2020.03.30.015446 AU - M Gasparetto AU - F Payne AU - K Nayak AU - J Kraiczy AU - C Glemas AU - Y Philip-McKenzie AU - A Ross AU - RD Edgar AU - D Zerbino AU - C Salvestrini AU - F Torrente AU - P Sarkies AU - R Heuschkel AU - M Zilbauer Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/03/31/2020.03.30.015446.abstract N2 - Background &amp; 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 dependant 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.AAVAnca Associated VasculitisCDCrohn’s DiseaseCpGCytosine – phosphate - GuanineDEGdifferentially expressed geneDNAmDNA methylationIBDInflammatory Bowel DiseaseMACSMagnetic Activated Cell SortingPBMCPeripheral Blood Mononuclear CellsPCDAIPediatric Crohn’s Disease Activity IndexPDCD1Programmed Cell Death 1PUCAIPediatric Ulcerative Colitis Activity IndexPCPrinciple ComponentSLESystemic Lupus ErythematosusUCUlcerative ColitisWGCNAweighted gene co-expression network analysis ER -