Transcription and DNA Methylation patterns of blood derived CD8+ T cells are associated with age and Inflammatory Bowel Disease but do not predict prognosis
| العنوان: | Transcription and DNA Methylation patterns of blood derived CD8+ T cells are associated with age and Inflammatory Bowel Disease but do not predict prognosis |
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| المؤلفون: | Judith Kraiczy, Matthias Zilbauer, Franco Torrente, Marco Gasparetto, Robert Heuschkel, Yosef Philip-McKenzie, Jack Satsangi, Nicholas T. Ventham, Felicity Payne, Claire Glemas, Daniel R. Zerbino, Rachel D. Edgar, Alexander Ross, Camilla Salvestrini, Rahul Kalla, Komal Nayak, Peter Sarkies |
| المصدر: | Gastroenterology |
| بيانات النشر: | by the AGA Institute, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, CD4-Positive T-Lymphocytes, Transcription, Genetic, Disease, CD8-Positive T-Lymphocytes, PDCD1, Programmed Cell Death 1, Inflammatory bowel disease, MACS, Magnetic Activated Cell Sorting, IBD, Inflammatory Bowel Disease, PC, Principle Component, 0302 clinical medicine, DEG, differentially expressed gene, Medicine, Child, PBMC, Peripheral Blood Mononuclear Cells, AAV, Anca Associated Vasculitis, validation, DNAm, DNA methylation, Crohn's disease, CpG, Cytosine – phosphate - Guanine, PCDAI, Pediatric Crohn’s Disease Activity Index, Gastroenterology, Age Factors, Ulcerative colitis, Child, Preschool, DNA methylation, Cohort, Biomarker (medicine), biomarker, 030211 gastroenterology & hepatology, Female, Single-Cell Analysis, epigenetic, Adult, medicine.medical_specialty, Adolescent, PUCAI, Pediatric Ulcerative Colitis Activity Index, Article, 03 medical and health sciences, Young Adult, Predictive Value of Tests, Internal medicine, WGCNA, weighted gene co-expression network analysis, Humans, Epigenetics, Hepatology, business.industry, SLE, Systemic Lupus Erythematosus, DNA Methylation, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, 030104 developmental biology, Case-Control Studies, UC, Ulcerative Colitis, Colitis, Ulcerative, prognosis, business, Biomarkers, CD, Crohn’s Disease |
| الوصف: | 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. Graphical abstract |
| اللغة: | English |
| تدمد: | 1528-0012 0016-5085 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e0919f104964294f126b6170de12b87fTest http://europepmc.org/articles/PMC7428744Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e0919f104964294f126b6170de12b87f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280012 00165085 |
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