P0125 Crohn’s-associated invariant T Cells are associated with disease severity and location and are not affected by medication intake

Background

Multiple alterations in the immune repertoire of IBD patients have been identified including, an expansion of a subset of type II natural killer T cells in CD patients, termed Crohn’s-associated invariant T cells (CAIT)1. Previously, we showed that CAIT cells respond to small molecules that resemble multiple microbial and drug metabolites2. This begs the question of whether CAIT cells are expanded due to the ongoing disease or the medications administrated to control the disease.

Methods

We profiled the T cell receptor alpha chain repertoire of 246 symptomatic controls, 228 treatment-naïve CD and 357 UC patients in addition to 176 and 329 treated CD and UC patients, respectively, from the Norwegian inception cohort IBSEN III3.

Results

Given that our cohort contained adult and paediatric IBD patients, we initially analysed the expansion of CAIT cells independently. Among adults, CAIT cells were significantly expanded in treatment-naïve CD patients (Fig. 1A) with a similar trend in paediatric patients (Fig. 1B) which arguably due to the small sample size was not significant. By combing the two groups, we observed a higher expansion of CAIT cells in treatment-naïve CD patients (Fig. 1C). The expansion of CAIT cells was also higher in treated-CD patients relative to controls and treated UC patients (Fig. 1D). By comparing the T cell repertoire of the UC and CD patients before and after treatment, we did not observe any significant difference in the expansion of CAIT cells due to medications (Fig. 1E, 1F).

CAIT cells were significantly expanded in ileocolonic and ileal CD patients relative to colonic CD patients and controls (Fig. 2A). This effect persisted in treated patients (Fig. 2B), additionally, the expansion of CAIT cells did not differ significantly in the same patient before treatment and after treatment (Fig. 2C). The expansion also correlated with the disease-behavior4, with patients suffering from a stricturing CD showing higher levels of CAIT expansion relative to controls and CD patients with non-stricturing, non-penetrating (NSNP) disease (Fig. 2D). After treatment, patients with a stricturing disease had a higher CAIT expansion relative to controls and also to NSNP patients (Fig. 2E). By comparing the expansion of CAIT cells in CD patients with NSNP disease before and after treatment, we did not observe any significant difference (Fig. 2F).

Conclusion

Our results indicate that CAIT cells are not induced by treatment and that disease severity and location strongly correlates with their expansion, future efforts shall focus on identifying the spatial distribution of CAIT cells in the gut tissues as well as identifying potential antigens driving their expansion.

References

1.Rosati E., Martini GR., Pogorelyy M V., Minervina AA., Degenhardt F., Wendorff M., et al. A novel unconventional T cell population enriched in Crohn’s disease. Gut 2022;71(11):2194 LP – 2204. Doi: 10.1136/gutjnl-2021-325373.

2.Minervina AA., Pogorelyy M V., Paysen S., Luening U., Degenhardt F., Franke A., et al. Crohn’s-associated invariant T cells (CAITs) recognise small sulfonate molecules on CD1d. Gut 2022:gutjnl-2022-328684. Doi: 10.1136/gutjnl-2022-328684.

3.Kristensen VA., Opheim R., Perminow G., Huppertz-Hauss G., Detlie TE., Lund C., et al. Inflammatory bowel disease in South-Eastern Norway III (IBSEN III): a new population-based inception cohort study from South-Eastern Norway. Scand J Gastroenterol 2021;56(8):899–905. Doi: 10.1080/00365521.2021.1922746.

4.Satsangi J., Silverberg MS., Vermeire S., Colombel J-F. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006;55(6):749. Doi: 10.1136/gut.2005.082909.