R M Corcoran1,2, P MacDonagh1,2, F O'Connell2,3, M E Morrissey2,3, M R Dunne2,3, R Argue1, J O'Sullivan2,3, D Kevans4,5,6. 1. Department of Gastroenterology, St. James's Hospital, Dublin, Ireland. 2. Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, Dublin 8, Ireland. 3. Trinity St. James's Cancer Institute, James's Street, Dublin 8, Ireland. 4. Department of Gastroenterology, St. James's Hospital, Dublin, Ireland. DKevans@stjames.ie. 5. Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, Dublin 8, Ireland. DKevans@stjames.ie. 6. School of Medicine, Trinity College Dublin, Dublin 2, Ireland. DKevans@stjames.ie.
Abstract
BACKGROUND: The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour. METHODS: UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated. p values < 0.05 were considered significant in analyses. RESULTS: Twenty-four UC patients were included (age [median, range]) 55 [21-72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression, p = 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (p = 0.015) and IL-12 / IL-23p40 (p = 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (p = 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (p = 0.016). CONCLUSION: Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.
BACKGROUND: The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour. METHODS: UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated. p values < 0.05 were considered significant in analyses. RESULTS: Twenty-four UC patients were included (age [median, range]) 55 [21-72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression, p = 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (p = 0.015) and IL-12 / IL-23p40 (p = 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (p = 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (p = 0.016). CONCLUSION: Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.
Authors: Jean Frédéric Colombel; Paul Rutgeerts; Walter Reinisch; Dirk Esser; Yanxin Wang; Yinghua Lang; Colleen W Marano; Richard Strauss; Björn J Oddens; Brian G Feagan; Stephen B Hanauer; Gary R Lichtenstein; Daniel Present; Bruce E Sands; William J Sandborn Journal: Gastroenterology Date: 2011-06-30 Impact factor: 22.682
Authors: Adrian G Murphy; Rory Casey; Aoife Maguire; Miriam Tosetto; Clare T Butler; Emer Conroy; Alison L Reynolds; Kieran Sheahan; Diarmuid O'Donoghue; William M Gallagher; David Fennelly; Breandán N Kennedy; Jacintha O'Sullivan Journal: Sci Rep Date: 2016-10-14 Impact factor: 4.379
Authors: Ian R Powley; Meeta Patel; Gareth Miles; Howard Pringle; Lynne Howells; Anne Thomas; Catherine Kettleborough; Justin Bryans; Tim Hammonds; Marion MacFarlane; Catrin Pritchard Journal: Br J Cancer Date: 2020-01-02 Impact factor: 7.640