Background & Aims Gene expression patterns of CD8 + T cells have been reported to correlate with clinical outcomes of adults with inflammatory bowel diseases (IBD). We aimed at validating these findings in independent patient cohorts. Methods We obtained peripheral blood samples from 112 children with a new diagnosis of IBD (71 with Crohn’s disease and 41 with ulcerative colitis) and 19 children without IBD (controls) and recorded medical information on disease activity and outcomes. CD8 + T cells were isolated from blood samples by magnetic bead sorting at the point of diagnosis and during the course of disease. Genome-wide transcription (n=192) and DNA methylation (n=66) profiles were generated using Affymetrix and Illumina arrays, respectively. Publicly available transcriptomes and DNA methylomes of CD8 + T cells from three adult patient cohorts with and without IBD were included in data analyses. Results Previously reported CD8 + T cell prognostic expression and exhaustion signatures were only found in the original adult IBD patient cohort. These signatures could not be detected either in a pediatric, or in a second adult IBD cohort. In contrast, an association between CD8 + T cell gene expression with age and sex was detected across all three cohorts. CD8 + gene transcription was clearly associated with IBD in the two cohorts that included non-IBD controls. Lastly, DNA methylation profiles of CD8 + T cells from children with Crohn’s disease correlated with age but not with disease outcome. Conclusions We were unable to validate previously reported findings of an association between CD8 + T cell gene transcription and disease outcome in IBD. Our findings reveal the challenges of developing prognostic biomarkers for patients with IBD and the importance of their validation in large, independent cohorts before clinical application.
The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid diagnostics, novel therapeutics, use of technology to track patients and vaccine development. Here, we describe our experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom. We encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. We overcame these by setting up a project team that included key members from all three organisations that met at least daily by teleconference. This group together worked to identify the best practices and procedures and to harmonise and cascade these to the wider trial team. This enabled us to set up the trial within 25 days and to recruit and vaccinate the participants within a further 23 days. The lessons learned from our experiences could be used to inform the conduct of clinical trials during a future infectious disease pandemic or public health emergency.
The authors would like to thank Natalia Savinykh Yarkoni at the at NIHR Cambridge BRC Cell Phenotyping Hub for her support with cell sorting. Furthermore, we express our gratitude towards all patients and their parents who have participated in this study. We thank Bella's Fund for their support and contribution towards raising awareness for childhood IBD and charity funding for the project. We would like to thank pediatric anaesthetists at Cambridge University Hospitals for their help with obtaining blood samples from patients. We are also very grateful for the helpful discussions and guidance on data analysis provided
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