Characterization of T-cell Receptor Repertoire in Inflamed Tissues of Patients with Crohn's Disease Through Deep Sequencing. Issue 6 (June 2016)

• Record Type: Journal Article
• Authors: Chapman, Christopher G.; Yamaguchi, Rui; Tamura, Kenji; Weidner, Jerome; Imoto, Seiya; Kwon, John; Fang, Hua; Yew, Poh Yin; Marino, Susana R.; Miyano, Satoru; Nakamura, Yusuke; Kiyotani, Kazuma
• Is Part Of: Inflammatory bowel diseases. Volume 22:Issue 6(2016:Jun.)
• Publication Date: 2016-06
• Subjects: immune regulation -- NGS -- inflammatory bowel diseases -- IBD -- genetic; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000752
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: Intestinal tissues of patients with Crohn's disease (CD) contain expanded populations of T cells which are believed to mediate inflammation. We performed a detailed characterization of these T-cell repertoires. Methods: We obtained biopsies from the neoterminal ileum of 12 patients undergoing evaluation for postoperative recurrent CD and 4 individuals with normal terminal ileum and no history of inflammatory bowel disease (controls). Samples of diseased terminal ileum were obtained from 5 patients undergoing surgery for stricturing or penetrating CD. Total RNA was extracted from tissues and peripheral blood mononuclear cells, and cDNAs were generated. We used next-generation sequencing to characterize T-cell receptor (TCR)-α and TCR-β cDNAs in ileal mucosal tissue and matched peripheral blood mononuclear cells of 17 patients with CD to identify oligoclonal expansions of T-cell populations associated with CD. Results: TCR diversity in mucosal tissue was significantly lower than that of matched peripheral blood mononuclear cells, indicating expansion of certain T-cell populations in inflamed intestinal tissue. A single TCR-β clonotype, CASSWTNGEQYF ( TRBV10-1 - TRBJ2-7 ), was enriched at a frequency of 7.0% to 28.9% in the neoterminal ileum of 4 of 12 patients with recurrent CD. The abundance of this clonotype significantly correlated with the severity of disease recurrence, based on Rutgeerts score ( P = 0.015). Conclusions: Specific populations of T cells are expanded in the inflamed intestinal mucosa of patients with CD; their abundance correlates with severity of disease recurrence. Studies of these T cells could provide information about mechanisms of CD pathogenesis. Deep TCR sequencing is a powerful tool that rapidly provides in-depth, real-time assessment of the T-cell repertoire. Abstract : Supplemental Digital Content is Available in the Text.Article first published online 2 May 2016.