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P264. Crohn's disease endoscopic post-operative recurrence is associated with a cytotoxic CD8+ T cells enrichment in blood and gut lamina propria

G. Boschetti1, S. Nancey1, D. Moussata1, E. Cotte2, A.-L. Charlois3, I. Graber1, D. Kaiserlian4, B. Flourié1, 1Lyon-Sud Hospital, Gastroenterology, Pierre-Bénite, France, 2Lyon-Sud Hospital, Digestive Surgery, Pierre-Bénite, France, 3Lyon-Sud Hospital, Statistics, Pierre-Bénite, France, 4Inserm, U 851, Lyon, France

Background

Crohn's disease (CD) patients undergoing curative ileocolonic resection are at high risk of endoscopic recurrence that is highly predictive of further clinical relapse.

Identifying reliable non-invasive biomarkers associated with early post-operative endoscopic recurrence might be of particular interest for identifying Crohn's disease (CD) patients at high risk of post-operative clinical recurrence. Recent evidences in mouse models of colitis have emphasized that besides Th1-type CD4+ T cells, cytotoxic CD8+ T cells initiate gut inflammation, especially by releasing cytotoxic granules (granzyme B, perforin) leading to intestinal epithelial lesions. In human CD, the contribution of cytotoxic CD8+ T cells as initiators of disease recurrence remains unknown.

Methods

Thirty-seven CD patients (23 females, mean ages) who had undergone a curative ileocolonic resection were prospectively and clinically followed during one year. A blood sample was collected as well as an ileocolonoscopy with intestinal biopsies close to the ileum anastomosis was performed at 6 and 12 months post-surgery.

The frequencies of cytotoxic granzyme B+ or perforin+ CD8+T cells were analysed from freshly isolated leucocytes from blood and biopsies by flow cytometry, RT-PCR, immunohistochemistry with reference to the occurrence of an endoscopic recurrence (defined as a Rutgeerts score > i1).

Results

An early endoscopic recurrence at 6 months post-resection was detected in 12 out of 37 (33%) of patients and overally 26 out of 37 (70%) patients developed an endoscopic recurrence within one-year post-surgery. Higher mRNA of CD8, granzyme B and perforin as well as proinflammatory cytokines TNFα, IFNγ, IL-1β were detected in the perianastomotic LP of the ileum from CD patients who experienced an endoscopic recurrence compared with those in patients who stay in remission. Granzyme B or perforin CD8+ T cells were significantly enriched in freshly isolated PBL as well as in ileum LPL in endoscopically recurrent CD patients when compared with controls. Using the cutoff points of 45%, the overall accuracy with which the frequency of granzyme B+ or perforin+ CD8+ T cells is able to distinguish patients with or without postoperative endoscopic recurrence within one-year post-surgery was 77% and 83%, respectively.

Conclusion

A cytotoxic CD8+ T cell enrichment coincides with the occurrence of a one-year post-operative endoscopic recurrence in patients with CD.