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DOP35 Monitoring of mucosal T cells subsets under biotherapies in IBD: responders exhibit a phenotype similar to healthy controls

N. Hammoudi1, K. Perez1, D. Hassid1, M.L. Tran Minh1, J.M. Gornet1, C. Baudry1, N. Lourenco1, B. Gergaud2, V. Chardiny2, J. Bonnet1, L. Le Bourhis2, M. Allez1

1APHP Saint Louis, Gastroenterology, Paris, France, 2INSERM, Unité U1160, Paris, France

Background

A dysregulated T-cell response is involved in the pathophysiology of inflammatory bowel diseases (IBD). T cells expressing the NKG2D activation receptor are implicated. Here, we investigated changes in intestinal T lymphocyte subsets overtime in patients treated by biotherapy for active disease.

Methods

In this prospective single-centre study, patients with IBD who have started a biotherapy (Infliximab, Adalimumab, Golimumab, Vedolizumab, Ustekinumab) for active disease were included. Mucosal biopsies in the inflamed segment were taken during endoscopies before treatment initiation (W0) and in the same location 14 weeks (W14) and 52 weeks (W52) after inclusion. Control biopsies were taken from 16 patients without IBD (7 ileal and 9 colonic). Immunophenotyping of isolated lymphocytes was performed by flow cytometry at each timepoint. Correlation with endoscopic response was evaluated. For Crohn’s disease (CD), the response was defined by a 50% decrease of the CDEIS score. For ulcerative colitis (UC), the response was defined by a 2 points decrease of the UCEIS

Results

Between February 2016 and November 2018, 85 patients were included. Forty-four were male (52%). Forty had an active CD with the most inflamed segment located for 28 in the colon and 12 in the ileum. Thirty-nine patients had active UC and 6 pouchitis. An anti-TNF was started for 51 patients (60%), Vedolizumab for 16 patients (19%) and Ustekinumab for 18 (21%). Lymphocytes phenotyping was performed at inclusion for the whole cohort, at W14 for 67 patients (79%) and at W52 for 49 patients (58%). Data concerning endoscopic response was available for all patients.

At W0, IBD patients displayed higher rates of CD4 T cells and lower rates of CD8 T cells than controls (medians: 31% vs. 48% for CD4, p < 0.001 and 52% vs. 37% for CD8, p < 0.001 respectively). Endoscopic responders experienced a normalisation of these mucosal populations as compared with non-responders (W14: 58% vs. 45% for CD4, p = 0.005 and 40% vs. 28% for CD8, p = 0.03; W52 56% vs. 43% for CD4, p = 0.01 and 27 vs. 43% for CD8, p = 0.003). Results remained significant when splitting the cohort in CD and UC patients. Before treatment initiation, IBD patients displayed lower expression of NKG2D on CD8 T cells (78% vs. 94%, p < 0.001). At W52, endoscopic responders presented significantly higher expression of this marker on CD8 T cells compared with non-responders (85% vs. 68%, p < 0.001). Results remained significant in UC and CD patients.

Conclusion

The intestinal T cells of IBD patients with active disease present an increase of the CD4 to CD8 T-cell ratio and lower expression of NKG2D on CD8 T cells reflecting engagement of this receptor in inflammation. These T-cell parameters are normalised in endoscopic responders but not in non-responders

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