P057 HLA B27 transgenic rat: a new animal model of postsurgical ileitis in inflammatory bowel disease
A. Chau*1, C. Chater1, S. Speca2, M. Djouina2, C. Dubuquoy2, L. Dubuquoy2, C. Neut3, D. Koriche1, P. Zerbib1, F.R. Pruvot1, P. Desreumaux4, B. Pariente4
1Lille University North of France, INSERM U995, Department of Digestive Surgery and Transplantation, CHRU Lille, Lille, France, 2Lille University North of France, INSERM U995, CHRU Lille, Lille, France, 3Lille University North of France, INSERM U995, Department of Microbiology, Faculty of Pharmacy, Lille, France, 4Hepato-Gastroenterology Department, Claude Huriez Hospital, University of Lille 2, Inserm Unit 995, University of Lille 2, Lille, France
Ileal recurrence of Crohn’s disease (CD) after ileocaecal resection (ICR) concerns the vast majority of the patients within the years after surgery. Mechanisms and predictive factors of recurrence remain unclear. The aim of the present study was to develop a reproducible animal model of ileal recurrence of postoperative CD in HLA B27 rats.
Seventy-two rats (28 male; 44 female) were enrolled, including 34 transgenic HLAB27 (Tg) rats and 38 non-transgenic wild-type (nTg) rats. At 12 week, 29 rats (14 Tg, 15 nTg) underwent ICR with ileo-colonic anastomosis compared with 19 rats (8 Tg, 11 nTg) who underwent a section-anastomosis of the small intestine (SAS) and 24 rats (12 Tg, 12 nTg) who underwent an open surgery without intestinal resection (OS). Rats were monitored daily clinically and were sacrificed 6 weeks after surgery (at 18 weeks). At the sacrifice in rats with ICR, ileal recurrence was double-blind assessed macroscopically by a small intestine score (0–4) by 2 independent investigators. Histological analysis (Ameho score 0 to 6) and mucosal cytokine production assessed by quantitative real-time polymerase chain reaction (PCR) were also performed at the sacrifice. Finally, influence of the intestinal microbiota in ileal recurrence was evaluated.
After ICR a macroscopic ileal recurrence was observed in 100% (14/14) of Tg rats, compared with 0% (0/15) of nTg rats (p < 0.0001). This recurrence was characterised by hyperemia of the ileal mucosa in 100% (14/14) and by ulcerations in more than 80% (12/14) of Tg animals (n = 12/14). Macroscopically, the score of the small intestine was 3 to 4 in Tg rats with ICR. No significant ileal lesion was observed in Tg and nTg rats who underwent SAS (n = 19) and OS (n = 24), with a macroscopic score of the small intestine less than to 2 (p <0.05). In rats with IRC, histological Ameho score was significantly higher in Tg rats (score of 4 to 6) compared with nTg rats (score 1 to 2, p <0.05). Messenger RNAs expressions of TNF, IL17, and IL1β above anastomotic ileum were also significantly higher in Tg rats (p < 0.05). Clostridium difficile and Clostridium perfringens were identified only in the intestinal microbiota of Tg rats and were correlated with macroscopic and histological lesion.
ICR in genetically predisposed HLA B27 rats is associated in 100% of cases with a macroscopic, histologic, and molecular recurrence in the terminal ileum 6 weeks after surgery. This recurrence is associated with the presence of Clostridium difficile and Clostridium perfringens. This new animal model shares strong physiopathologic similarities with postoperative recurrence in CD patients. It permits us to understand better the mechanisms involved in CD development, and develop new therapeutic strategies.