P249 Colonic Explant Lactate Concentration and Disease Progression in Ulcerative Colitis
McShane, C.(1,2)*;Corcoran, R.(1,2);O'Connell, F.(2);MacDonagh, P.(1,2);O'Sullivan, J.(2,3);Kevans, D.(4,5);
(1)St James's Hospital, Department of Gastroenterology, Dublin, Ireland;(2)Trinity Translational Medicine Institute- St. James’s Hospital and Trinity College Dublin, Department of Surgery, Dublin, Ireland;(3)Trinity College Dublin, St. James’s Cancer Institute, Dublin, Ireland;(4)St. James’s Hospital, Department of Gastroenterology, Dublin, Ireland;(5)Trinity College Dublin, School of Medicine, Dublin, Ireland;
Background
There is therefore an unmet need for biomarkers of ulcerative colitis (UC) disease behaviour and clinical response. Lactate is known to have immunoregulatory effects. Recent studies have demonstrated that lactate concentrations are decreased in colonic tissue of patients with inflammatory bowel disease. 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.
Methods
UC patients were prospectively recruited in 2 cohorts: discovery (2018 – 2019) and validation (2020 - 2021). Endoscopic biopsies were collected from the sigmoid colon and TCM generated as per previously described methods. Total protein content of biopsies was quantified to allow normalisation of secretions. TCM secreted lactate was quantified using a colorimetric L-Lactate assay (Abcam, UK). Patients demographics, baseline characteristics and disease behaviour were characterised. 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. P values < 0.05 were considered significant in analyses.
Results
52 patients were included in the study (discovery cohort n=28, replication cohort n=24), baseline characteristics of each cohort are described in figure 1. No differences in TCM lactate concentration were observed in patients segregated by endoscopic Mayo score, disease duration and biologic exposure status. [Figure 2]. In the discovery cohort, patients in the lowest quartile of TCM lactate concentration had a shorter time to disease progression, p=0.005. This observation was not replicated in the validation cohort, p=0.79 [Figure 3]. Multivariate analysis demonstrated clinical remission was the only variable independently associated with time to disease progression in the discovery cohort (HR 0.17 (95% CI 0.05 – 0.66), p= 0.004). Endoscopic remission was the only variable independently associated with time to disease progression in the validation cohort (HR 0.21 (95% CI 0.06 – 0.81), p = 0.02).
Conclusion
Lactate is produced in high amounts by innate immune cells on inflammatory activation. UC TCM lactate concentration was not associated with endoscopic severity and was not reproducibly associated with disease progression in discovery or replication cohorts.