TBA (22W164)

Colonic Explant Lactate Concentration and Disease Progression in Ulcerative Colitis

Author(s)

C McShane, F O’Connell, R Corcoron, P MacDonagh, J O’Sullivan, D Kevans

Department(s)/Institutions

1. Department of Gastroenterology, St James's Hospital, Dublin 8 2. Trinity Translational Medicine Institute, Trinity College Dublin 3. Department of Surgery, Trinity College Dublin, St James’s Hospital Dublin 8

Introduction

Lactate is now known to have immunomodulatory effects. Recent studies have demonstrated that lactic acid concentrations are decreased in colonic tissue of ulcerative colitis (UC) patients.

Aims/Background

We aimed to investigate if lactate concentration in tissue cultured media (TCM) from UC patient-derived colonic explants is associated with endoscopic disease severity and disease progression.

Method

UC patients were prospectively recruited. Endoscopic biopsies were collected from the sigmoid colon and TCM generated as per previously described methods. Endoscopic disease severity was categorised by endoscopic Mayo score. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent in follow-up period. TCM secreted lactate was quantified using a colorimetric L-Lactate assay (Abcam, UK).

Results

52 patients were recruited (discovery cohort n=28, replication cohort n=24); age [median,IQR] 44.5, 33.75 - 60.75 years; 50% male; disease duration [median,IQR] 7.5, 3.3 - 17.3 years. 40% were receiving biologic therapy. Endoscopic Mayo score [median, range] 1 0–3. Disease progression occurred in 59.6% of patients. Follow up [median,IQR] 38.57, 5.9 – 75.7 weeks. No significant association between TCM lactate concentration and endoscopic severity was observed in discovery or replication cohorts. No significant association was observed between TCM lactate concentration and disease progression or progression-free survival in discovery or replication cohorts.

Conclusions

Lactate is produced in high amounts by innate immune cells on inflammatory activation. UC TCM lactate concentration was not associated with endoscopic severity or disease progression in discovery or replication cohorts.