M. Laffin2, T. Perry2, B. Dicken2, R. Fedorak3, K. Madsen3 1University Of Alberta,Edmonton, AB, Canada 2University Of Alberta,Department Of Surgery,Edmonton, AB, Canada 3University Of Alberta,Department Of Medicine,Edmonton, AB, Canada
Introduction: Crohn’s disease (CD), is a type of inflammatory bowel disease, defined by transmural inflammation of the alimentary tract. Complications of CD leads to intestinal resection in the majority of patients during their lifetime. While CD can affect any segment of the intestinal tract, it is most often found in the ileocecal region, making Ileocolic resection the most common procedure performed. Unfortunately, after resection of the diseased segment, inflammation almost inevitably returns proximal to the surgical anastomosis in the neo-terminal ileum. Studying this recurrence may offer a glimpse into the pathophysiology and development of the disease. To date, few published results examine the inflammatory milieu of the peri-operative CD patient and how that profile relates to recurrence.
The objective of our study is to define the immunologic environment of the gut at the time of surgery which and identified how it is associated with post-operative recurrence.
Methods: 26 CD patients were recruited at the time of Ileocolic resection and followed prospectively. Mesenteric lymph node (MLN) and mucosal samples from the terminal ileum were snap frozen in the operating theatre. All patients received follow-up ileocolonoscopy six months post-operatively, at which time recurrence scores in the neo-terminal ileum were recorded using the Rutgeert’s scale. Endoscopic recurrence was defined as a score ≥ 2. A comprehensive multiplex immune assay utilizing the MesoScale Discovery platform measured tissue concentrations of 31 cytokines and chemokines. Known clinical characteristics associated with recurrence were tested using the Fisher’s exact test. Individual analytes were compared using the Mann-Whitney-U test.
Results: 30% of patients had endoscopic disease recurrence at follow up. Mean time to ileocolonoscopy was 209 days in the recurrence group vs. 176 days in the remission group. Clinical parameters including fistulizing disease, previous surgery, and smoking were not significantly associated with recurrence after 6 months in our cohort. When patients were stratified based on these clinical parameters mucosal IL-6 was associated with stricturing disease, smoking was associated with elevated mucosal IL-6 and IL-1α, and perianal disease was associated with elevated mucosal TNF-α, IL-6, IL-1β, and IFN-γ.
When analytes were evaluated by post-operative recurrence, elevated MCP-1 in the mucosa of surgical specimens was associated with disease recurrence. An elevated level of IL-5 and IL-16 was seen in the MLN of patients who recurred.
Conclusion: Results from this study suggest that chemokines are a factor in post-operative recurrence as MCP-1, IL-5 and IL-16 all act as prominent chemoattractants to various immune cell types. These observations highlight the need for further study in cell recruitment to the gut, and its relationship to post-operative recurrence.