T cell clonal expansions in ileal Crohn's disease are associated with smoking behaviour and postoperative recurrence. Issue 11 (12th February 2019)

• Record Type: Journal Article
• Authors: Allez, Matthieu; Auzolle, Claire; Ngollo, Marjolaine; Bottois, Hugo; Chardiny, Victor; Corraliza, Ana Maria; Salas, Azucena; Perez, Kevin; Stefanescu, Carmen; Nancey, Stéphane; Buisson, Anthony; Pariente, Benjamin; Fumery, Mathurin; Sokol, Harry; Tréton, Xavier; Barnich, Nicolas; Seksik, Philippe; Le Bourhis, Lionel
• Other Names: author non-byline.; Cattan Pierre author non-byline.; Chirica Mircea author non-byline.; Munoz-Bongrand Nicolas author non-byline.; Corte Hélène author non-byline.; Gornet Jean-Marc author non-byline.; Baudry Clotilde author non-byline.; Lourenco Nelson author non-byline.; Maillet Mariane author non-byline.; Tran-Minh My-Linh author non-byline.; Nisard Andrée author non-byline.; Beaugerie Laurent author non-byline.; Bourrier Anne author non-byline.; Nion-larmurier Isabelle author non-byline.; Landman Cecilia author non-byline.; Rajca Sylvie author non-byline.; Quevrain Elodie author non-byline.; Brot Loic author non-byline.; Chafai Najim author non-byline.; Lefevre Jeremie author non-byline.; Tiret Emmanuel author non-byline.; Svreck Magali author non-byline.; Hoyau-idrissi Nadia author non-byline.; Flejou Jean François author non-byline.; Guedj Nathalie author non-byline.; Panis Yves author non-byline.; Magiorri Leon author non-byline.; Feron Mariane author non-byline.; Bouhnik Yoram author non-byline.; Corcos Olivier author non-byline.; Cazals-hatem Dominique author non-byline.; Dray Xavier author non-byline.; Chaput Ulrika author non-byline.; Marteau Philippe author non-byline.; Bommelaer Gilles author non-byline.; Goutte Marion author non-byline.; Vazeille Emilie author non-byline.; Rodrigues Michael author non-byline.; Sauvanet Pierre author non-byline.; Desreumaux Pierre author non-byline.; Nachury Maria author non-byline.; Sommeville Coralie author non-byline.; Dupas Jean-Louis author non-byline.; Brazier Franck author non-byline.; Chatelain Denis author non-byline.; Attencourt Christophe author non-byline.; Sabbagh Charles author non-byline.; Leconte Martine author non-byline.; Boschetti Gilles author non-byline.; Flourié Bernard author non-byline.; François Yves author non-byline.; Cotte Eddy author non-byline.; Charlois Anne-laure author non-byline.; Falgon Peggy author non-byline.; Moussata Driffa author non-byline.; Chauvenet Marion author non-byline.; Boyer Sarah author non-byline.; Hebuterne Xavier author non-byline.; Filippi Jérome author non-byline.; Hofmann Paul author non-byline.; Bezeault Madeleine author non-byline.; Margalef Carole author non-byline.; Detre Patricia author non-byline.;
• Is Part Of: Gut. Volume 68:Issue 11(2019)
• Page Start: 1961
• Page End: 1970
• Publication Date: 2019-02-12
• Subjects: ibd -- crohn's disease -- surgery for ibd -- t-cell receptor; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2018-317878
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : T cell clonal expansions are present in the inflamed mucosa of patients with Crohn's disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection. Methods: T cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively. Results: TCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment. Conclusion: Clonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven. Trial registration number: NCT03458195.