Profoundly Expanded T-cell Clones in the Inflamed and Uninflamed Intestine of Patients With Crohn's Disease
| Autor: | A. H. C. van Kampen, Liset Westera, G. D'Haens, A. A. Te Velde, R.E. Esveldt, Charlotte P. Peters, Esther W M Vogels, Frank Baas, Marieke E. Doorenspleet, G. R. van den Brink, C.Y. Ponsioen, W. A. Bemelman, Theodorus B. M. Hakvoort, N. de Vries, Christianne J. Buskens |
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| Přispěvatelé: | AII - Inflammatory diseases, Clinical Immunology and Rheumatology, Tytgat Institute for Liver and Intestinal Research, APH - Personalized Medicine, APH - Methodology, Epidemiology and Data Science, Genome Analysis, Other departments, Surgery, Gastroenterology and Hepatology, Experimental Immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Budesonide Adult Male medicine.medical_specialty Colon Biopsy T-Lymphocytes Anti-Inflammatory Agents Receptors Antigen T-Cell Inflammatory bowel disease Gastroenterology Severity of Illness Index 03 medical and health sciences Young Adult 0302 clinical medicine Crohn Disease Gastrointestinal Agents Ileum Internal medicine Adalimumab Medicine Humans Inflammation Crohn's disease Gastrointestinal agent medicine.diagnostic_test business.industry Repertoire General Medicine Middle Aged medicine.disease digestive system diseases Infliximab Clone Cells 030104 developmental biology C-Reactive Protein Case-Control Studies Immunology 030211 gastroenterology & hepatology Female business medicine.drug |
| Zdroj: | Journal of Crohn s & colitis, 11(7), 831-839. Elsevier |
| ISSN: | 1876-4479 1873-9946 |
| Popis: | T cells are key players in the chronic intestinal inflammation that characterises Crohn's disease. Here we aim to map the intestinal T-cell receptor [TCR] repertoire in patients with Crohn's disease, using next-generation sequencing technology to examine the clonality of the T-cell compartment in relation to mucosal inflammation and response to therapy. Biopsies were taken from endoscopically inflamed and uninflamed ileum and colon of 19 patients with Crohn's disease. From this cohort, additional biopsies were taken after 8 weeks of remission induction therapy from eight responders and eight non-responders. Control biopsies from 11 patients without inflammatory bowel disease [IBD] were included. The TCRβ repertoire was analysed by next-generation sequencing of biopsy RNA. Both in Crohn's disease patients and in non-IBD controls, a broad intestinal T-cell repertoire was found, with a considerable part consisting of expanded clones. Clones in Crohn's disease were more expanded [p = 0.008], with the largest clones representing up to as much as 58% of the total repertoire. There was a substantial overlap of the repertoire between inflamed and uninflamed tissue and between ileum and colon. Following therapy, responders showed larger changes in the T-cell repertoire than non-responders, although a considerable part of the repertoire remained unchanged in both groups. The intestinal T-cell repertoire distribution in Crohn's disease is different from that in the normal gut, containing profoundly expanded T-cell clones that take up a large part of the repertoire. The T-cell repertoire is fairly stable regardless of endoscopic mucosal inflammation or response to therapy |
| Databáze: | OpenAIRE |
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