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P043. MMPs in pouch in pediatric onset IBD – Diagnostic clues and markers for inflammation

L. Mäkitalo1, M.L. Piekkala2, R. Rintala2, M. Ashorn3, M. Pakarinen2, A. Koivusalo2, R. Karikoski4, J. Natunen2, U. Saarialho-Kere (deceased)1,5, K. Kolho2

1Department of Dermatology, Helsinki University Central Hospital and Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; 2Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland; 3Department of Pediatrics, Tampere University Hospital, Tampere, Finland; 4HUSLAB, Helsinki University Central Hospital, Helsinki, Finland; 5Department of Clinical Science and Education and Section of Dermatology, Karolinska Institutet at Stockholm Söder Hospital, Stockholm, Sweden

Aim: The origin of inflammation in the pouch – a frequent complication after colectomy in inflammatory bowel disease (IBD) – is poorly understood. Matrix metalloproteinases (MMPs) are enzymes involved in the pathogenesis of mucosal damage in IBD. We examined the MMP- and TIMP-profiles in pouch biopsies in children with pediatric onset IBD, and assessed whether these profiles reflect an IBD or non-IBD type of mucosal changes in the pouch.

Figure 1. MMP-7 and MMP-3 in UC in lower (A, C, respectively) and higher grade of inflammation and calprotectin levels (B, D, respectively). TIMP-2 in UC (E) and CD (F). Thin arrows depict plasma cells, thick arrows macrophages, bent arrows eosinophils, and serpentine arrows endothelium (b,b′,d,d′,d″,e).

Material and Methods: We studied expression of MMPs-3, -7, -8, -9, -12, -26, and TIMPs-1, -2, -3 by immunohistochemistry in ileal pouch samples of 35 pediatric onset IBD patients (UC, n = 28, and CD, n = 7) with a median duration of 13 years from surgery. MMP and TIMP expression was related to inflammatory markers, fecal calprotectin, ESR and CRP, and to the histological grade of inflammation.

Results: Most pouch samples showed expression of epithelial and stromal MMP-3, -7, -12, TIMP-2 and -3 (Figs 1,2). In samples with low inflammatory activity in histological assessment, MMP-7 expression in epithelium was increased compared to samples with active inflammation (p < 0.05) (Figs 1A,B). Similarly, MMP-3 expression in epithelium was related to lower degree of inflammatory cell infiltrate (p < 0.05) (Figs 1C,D). UC samples had higher epithelial (p < 0.05) and stromal (p < 0.05) TIMP-2 expression compared to CD samples (Figs 1E,F) possibly guiding diagnostics in unclear cases. Unlike the normal ileum, TIMP-3 (Figs 2A,B) and MMP-12 (Fig 2C) were found in the majority of samples, in line with IBD related colitis.

Figure 2. TIMP-3 in UC (A), and in CD (B). MMP-12 expression shown here in a CD sample (C). Thin arrows depict plasma cells, thick arrows macrophages, and serpentine arrows endothelium (a,a′).

Conclusion: We suggest that MMPs-3, -7, -12, and TIMP-2 and -3 are important in pouch mucosa. Further, epithelial MMP-3 and MMP-7 and TIMP-2 may aid in characterizing inflammatory changes in pouch. MMP expression in the pouch shares some similarities with previously reported expression in colonic IBD.