P0012 The predictive value of the mesorectal macrophage profile for pouch outcomes in ulcerative colitis
Authors: Haanappel A , van der Does de Willebois E , Becker M , Vlug M , Bemelman W , Buskens C , Wildenberg M 
Published: January 2025

Abstract

Background
In patients with ileal pouch-anal anastomosis (IPAA), pouch failure may occur as a result of inflammatory activity in the pouch (e.g. pouchitis or Crohn’s disease [CD]). Moreover, the inflammatory status of mesenteric macrophages in CD patients has been related to postoperative outcomes. Prior research has identified a pro-inflammatory macrophage composition in the mesorectum of CD patients, and resection of this proinflammatory tissue during proctectomy reduces postoperative complications.(1) This study aimed to evaluate whether the mesenteric macrophage profile in patients undergoing IPAA is predictive of postoperative pouch outcomes.

Methods
Mesenteric samples were collected from patients undergoing modified two stage IPAA, during (subtotal-) colectomy or completion proctectomy. The macrophage profile was determined by flow cytometry as CD45+ CD66b-CD14+ cells and divided into regulatory (CD206+) or pro-inflammatory macrophages (CD206-). Given previous findings that M1 macrophages (pro-inflammatory) produce high levels of calprotectin, mesenteric calprotectin levels were measured by routine standard in the clinical lab as a proxy for inflammatory macrophage activity. (2)

Results
Mesenteric tissue was collected in 16 patients (4/16 colectomy, and 12/16 completion proctectomy with IPAA), with a median follow-up 54.5 months. In patients who developed pouch related complications (i.e pouchitis, CD in the pouch or other dysfunction), the ratio of regulatory (CD206+ expressing) to pro-inflammatory (CD206-) macrophages was significantly decreased (ratio 0.38 vs 0.14, p=0.01), indicating a more pro-inflammatory phenotype [Figure 1]. In addition, we observed an inverse correlation between calprotectin levels and the M2/M1 ratio.

Conclusion
The inflammatory state of mesorectal macrophages can be correlated to postoperative outcomes in patients undergoing IPAA surgery. Preliminary data from this study demonstrate that patients with a more pro-inflammatory macrophage phenotype in the mesentery seem to be of concern in terms of pouch outcomes. In addition, a correlation was observed between the M2/M1 macrophage ratio and calprotectin levels. Further research is needed to evaluate if mesenteric calprotectin could function as a prognostic marker to predict postoperative outcomes in IBD patients.

References
1.de Groof EJ, van der Meer JHM, Tanis PJ, de Bruyn JR, van Ruler O, D'Haens G, et al. Persistent Mesorectal Inflammatory Activity is Associated With Complications After Proctectomy in Crohn's Disease. J Crohns Colitis. 2019;13(3):285-93.
2.Bloemendaal FM, Becker M, Koelink PJ, van der Bilt JD, Bemelman WA, D’Haens GRAM, et al. DOP82 Macrophages in Crohn’s disease mesentery are predominantly inflammatory and produce calprotectin. Journal of Crohn's and Colitis. 2020;14(Supplement_1):S121-S2.

Figure 1. The ratio of regulatory (CD206) to pro-inflammatory (CD206-) macrophages in patients with and without disease complications (Ratio 0.38 vs 0.14, p=0.01)