P084 Secreted inflammatory protein profiles following treatment of ex-vivo human Ulcerative Colitis and Crohn’s Disease explants with licenced biologic therapies
Corcoran, R.(1);O'Connell, F.(2);O'Sullivan, J.(2);Kevans, D.(1);
(1)St James’s Hospital, Department of Gastroenterology, Dublin, Ireland;(2)Trinity Translational Medicine Institute- Trinity College Dublin- Ireland, Department of Surgery, Dublin, Ireland;
Background
Patient-derived inflammatory bowel disease (IBD) ex-plants have potential for biomarker and therapy discovery. Treatment of IBD ex-plants ex-vivo with licensed biologic therapies may result in further insights into their mechanism of action.
Methods
We aimed to evaluate the effect of Infliximab (IFX), Ustekinumab (USTK) and Vedolizumab (VDZ) on inflammatory protein secretion profiles in ex-vivo human IBD ex-plants.
Patients with IBD, undergoing endoscopy, were prospectively recruited. Endoscopic biopsies were collected from the sigmoid colon and IBD ex-plants generated as per previously described methods. IBD ex-plants were then co-cultured for 24 hours with an IgG control vehicle, IFX, USTK and VDZ. After 24 hours, tissue conditioned media (TCM) from IBD ex-plants was collected. TCM secreted inflammatory protein profiles were quantified using 54 V-plex ELISA (Meso Scale Diagnostics, USA). Secreted inflammatory protein profiles were compared between IgG vehicle (control) and USTK, IFX, VDZ treated ex-plants. All continuous variables are presented as median [interquartile range (IQR)]. P values < 0.05 were considered significant in analyses.
Results
18 patients with Ulcerative Colitis (UC) and 19 patients with Crohn’s Disease (CD) were included; age (median, [IQR]) 41[33-53], years, 49% male; disease duration (median, [IQR]) 9 [5-14] years; 54% of patients were anti-TNF naïve. IL-22 secretion was significantly lower in UC explants treated with IFX compared with IgG control; 4.5 [3.1 – 39.9] versus 17.5 [10.3 – 98.3] pg/ml per ug of protein respectively, p=0.004. IL-22 secretion was significantly lower in UC explants treated with USTK compared with IgG control; 7.8 [1.9 – 26.5] versus 27.9 [10.3 – 110.7] pg/ml per ug of protein respectively, p=0.004. IL-22 secretion was significantly lower in UC ex-plants treated with VDZ compared with IgG control; 10.6 [3.2 – 35.7] versus 17.5 [10.2 – 73.5] pg/ml per ug of protein respectively, p=0.01. For CD explants, IL-22 secretion was significantly lower in USTK compared with IgG control; 24.4 [17.6 – 57.7] versus 211.7 [75.9 – 588.1] pg/ml per ug of protein respectively, p < 0.001. In UC and CD explants, IL-23 secretion was significantly decreased comparing USTK with IgG control treatments, p < 0.004 for all comparisons.
Conclusion
IBD ex-plant IL-22 secretion is reduced following biologic therapy particularly in patients with UC. IL-22 is a pleotropic cytokine considered an essential factor in intestinal immune-epithelial cross talk and is capable of both pro- and anti-inflammatory functions depending on tissue microenvironment including cytokine milieu. Further evaluation of the contribution of IL-22 to IBD disease biology is warranted.