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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

1
Amsterdam Rheumatology and immunology Center, Academic Medical Center, Amsterdam, The Netherlands.
2
Laboratory for Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
3
Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
4
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
5
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherland.
6
Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.

Abstract

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.

Methods:

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.

Results:

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.

Conclusions:

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.

KEYWORDS:

Crohn’s disease; TCR; next-generation sequencing

PMID:
28158397
DOI:
10.1093/ecco-jcc/jjx012
[Indexed for MEDLINE]

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