Gregor Novak1,2, Toer Stevens3, Tanja Van Viegen1, Peter Bossuyt4, Borut Štabuc2, Jenny Jeyarajah1, Guangyong Zou1,5, Ingrid C Gaemers6, Trevor D McKee7, Fred Fu7, Lisa M Shackelton1, Reena Khanna1,8, Gijs R van den Brink3,6, William J Sandborn1,9, Brian G Feagan1,5,8, Rish K Pai10, Vipul Jairath1,5,8, Niels Vande Casteele1,9, Geert D'Haens1,3. 1. Robarts Clinical Trials Inc, London, ON, Canada. 2. Department of Gastroenterology, Ljubljana University Medical Centre, University of Ljubljana, Ljubljana, Slovenia. 3. Inflammatory Bowel Disease Centre, Academic Medical Center, Amsterdam, The Netherlands. 4. Imelda General Hospital, Bonheiden, Belgium. 5. Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada. 6. Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands. 7. STTARR Innovation Centre, University Health Network, Toronto, ON, Canada. 8. Department of Medicine, University of Western Ontario, London, ON, Canada. 9. Department of Medicine, University of California San Diego, La Jolla, California. 10. Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona.
Abstract
BACKGROUND: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. AIM: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. METHODS: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. RESULTS: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. CONCLUSIONS: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.
BACKGROUND: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. AIM: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. METHODS: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. RESULTS: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. CONCLUSIONS: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.
Authors: Bryan Linggi; Vipul Jairath; Guangyong Zou; Lisa M Shackelton; Dermot P B McGovern; Azucena Salas; Bram Verstockt; Mark S Silverberg; Shadi Nayeri; Brian G Feagan; Niels Vande Casteele Journal: Sci Rep Date: 2021-09-14 Impact factor: 4.996