TBA (25W171)

Secreted inflammatory protein profiles of human inflammatory bowel disease explants following treatment ex-vivo with licenced biologic therapies and patients’ in-vivo response

Author(s)

RM Corcoran, F O’Connell, N Schellenberg, D Kevans, J O’Sullivan

Department(s)/Institutions

Department of Gastroenterology, St James’s Hospital, Dublin 8, Ireland Trinity Translational Medicine Institute, Trinity College Dublin, Ireland Department of Surgery, Trinity College Dublin, Dublin , Ireland

Introduction

Infliximab (IFX), ustekinumab (UST) and vedolizumab (VDZ) are biologics licenced for use in ulcerative colitis (UC) and Crohn’s disease (CD). Patient derived inflammatory bowel disease (IBD) explants have the potential to be used as a precision medicine tool.

Aims/Background

We aimed to evaluate the effect of IFX, UST and VDZ on inflammatory protein secretion profiles in ex-vivo human IBD ex-plants.

Method

Patients with IBD due to commence in-vivo biologic therapy were prospectively recruited. Endoscopic biopsies were collected and IBD explants generated as per previously described methods. IBD explants were then cultured for 24 hours with an IgG control vehicle, IFX, USTK and VDZ. Tissue conditioned media (TCM) from IBD explants 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 biologic treated explants. Principal component analysis (PCA) was carried out to characterise the influence of biologics on ex-vivo explant secreted inflammatory profiles.

Results

37 patients with were included (51% CD, 49% UC); age (median, [IQR]) 41[33-53] years, 49% male; disease duration (median, [IQR]) 9 [5-14] years. 23 patients were subsequently commenced on either IFX, UST or VDZ in vivo and followed over 2 years. PCA identified significant variation in the CD and UC secretome. Biologic therapy ex-vivo resulted in significant alterations and clustering in the UC secretome compared to control.

Conclusions

Treatment with licenced biologic therapies ex-vivo significantly alters multiple secreted proteins in IBD explants. Further study is required to completely understand the effects of licenced biologic therapies on the IBD tissue microenvironment.