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.
- crohn’s disease
- surgery for ibd
- t-cell receptor
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Contributors MA and LLB conceived and designed the project, interpreted data and wrote the manuscript. MA, CA, KP and LLB analysed TCR sequencing data. AMC and AS provided analysing scripts for TCR sequencing data. MA and CA organised and analysed clinical parameters. MN, VC and KP performed transcriptomic analyses. LLB, HB and VC performed cell isolation experiments. CS, SN, AB, BP, MF, HS, XT, NB and PS provided essential materials and were involved in discussions. REMIND investigators provided IBD patient samples and ethical approval for the project.
Funding This study was supported by grant from the Helmsley Charitable Trust, the Association Francois Aupetit and MSD France laboratories.
Competing interests MA received honoraria from Abbvie, MSD, Janssen, Takeda, Pfizer, Novartis, Ferring, Tillots, Celgene and Genentech/Roche. SN received honoraria from MSD, Abbvie, Takeda, Janssen, HAC Pharma, Tillots, Ferring and Novartis. AB received honoraria from MSD, Abbvie, Ferring, Takeda, Vifor Pharma, Sanofi‐Aventis, Hospira and Janssen. BP received honoraria from AbbVie, MSD, Takeda, Janssen, Bioagaran and Ferring. MF received honoraria from AbbVie, MSD, Takeda, Janssen, Pfizer, Ferring and Boehringer. HS received unrestricted study grants: Danone, Biocodex and Enterome; board membership, consultancy, or lecture fees: Carenity, Abbvie, Astellas, Danone, Ferring, Mayoly Spindler, MSD, Novartis, Roche, Tillots, Enterome, Maat, BiomX, Biose, Novartis and Takeda; cofunder of Nextbiotix. XT received honoraria from Abbvie, MSD, Takeda, Ferring, Norgine and Janssen. PS received honoraria from Takeda, MSD, Biocodex, Ferring and Abbvie, and non-financial support from Takeda. CA, MN, HB, VC, AMC, AS, CS and NB declare no competing interest.
Ethics approval The ethical committee of Hospital Saint-Louis approved this study (CPP#2009/17).
Provenance and peer review Not commissioned; externally peer reviewed.
Collaborators REMIND Study group (REMIND Study Group, France): Pierre Cattan; Mircea Chirica; Nicolas Munoz-Bongrand; Hélène Corte; Jean-Marc Gornet; Clotilde Baudry; Nelson Lourenco; Mariane Maillet; My-Linh Tran-Minh; Andrée Nisard; Laurent Beaugerie; Anne Bourrier; Isabelle Nion-Larmurier; Cecilia Landman; Sylvie Rajca; Elodie Quevrain; Loic Brot; Najim Chafai; Jeremie Lefevre; Emmanuel Tiret; Magali Svreck; Nadia Hoyau-Idrissi; Jean François Flejou; Nathalie Guedj; Yves Panis; Leon Magiorri; Mariane Feron; Yoram Bouhnik; Olivier Corcos; Dominique Cazals-Hatem; Xavier Dray; Ulrika Chaput; Philippe Marteau; Gilles Bommelaer; Marion Goutte; Emilie Vazeille; Michael Rodrigues; Pierre Sauvanet; Pierre Desreumaux; Maria Nachury; Coralie Sommeville; Jean-Louis Dupas; Franck Brazier; Denis Chatelain; Christophe Attencourt; Charles Sabbagh; Martine Leconte; Gilles Boschetti; Bernard Flourié; Yves François; Eddy Cotte; Anne-Laure Charlois; Peggy Falgon; Driffa Moussata; Marion Chauvenet; Sarah Boyer; Xavier Hebuterne; Jérome Filippi; Paul Hofmann; Madeleine Bezeault; Carole Margalef; and Patricia Detre.
Correction notice This article has been corrected since it published Online First. The author affiliation details have been corrected.
Patient consent for publication Obtained.