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J Crohns Colitis. 2017 Jul 1;11(7):831-839. doi: 10.1093/ecco-jcc/jjx012.

Profoundly Expanded T-cell Clones in the Inflamed and Uninflamed Intestine of Patients With Crohn's Disease.

Author information

Amsterdam Rheumatology and immunology Center, Academic Medical Center, Amsterdam, The Netherlands.
Laboratory for Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherland.
Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.


Background and Aim:

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.


Crohn’s disease; TCR; next-generation sequencing

[Indexed for MEDLINE]

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