Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 14, 2012; 18(30): 4028-4036
Published online Aug 14, 2012. doi: 10.3748/wjg.v18.i30.4028
Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis
Laura Mäkitalo, Maija Piekkala, Merja Ashorn, Mikko Pakarinen, Antti Koivusalo, Riitta Karikoski, Johanna Natunen, Ulpu Saarialho-Kere, Risto Rintala, Kaija-Leena Kolho
Laura Mäkitalo, Maija Piekkala, Mikko Pakarinen, Antti Koivusalo, Johanna Natunen, Risto Rintala, Kaija-Leena Kolho, Hospital for Children and Adolescents, Helsinki University Central Hospital, University of Helsinki, FIN-00029 Helsinki, Finland
Merja Ashorn, Department of Pediatrics, Tampere University Hospital, Teiskontie 35, 33521 Tampere, Finland
Riitta Karikoski, Department of Pathology, HUSLAB, Helsinki University Central Hospital, Haartmaninkatu 3, FI-00029 Helsinki, Finland
Ulpu Saarialho-Kere, Department of Clinical Science and Education and Section of Dermatology, Karolinska Institutet at Stockholm Söder Hospital, 11883 Stockholm, Sweden
Author contributions: Kolho KL and Saarialho-Kere U designed the study; Pakarinen M, Koivusalo A and Rintala R obtained the biopsies; Mäkitalo L, Piekkala M, Karikoski R and Saarialho-Kere U performed the histological analysis of samples; Mäkitalo L analyzed the data; Mäkitalo L, Piekkala M and Kolho KL prepared the manuscript; and all authors took part in the critical revision of the paper.
Supported by The Academy of Finland, Finska Läkaresällskapet, Helsinki University Central Hospital Research Fund, Finnish Cultural Foundation (to Mäkitalo L); Biomedicum Helsinki Foundation (to Mäkitalo L), Finland; the Swedish Research Council, Sweden (to Saarialho-Kere U); the Päivikki and Sakari Sohlberg Foundation (to Kolho KL); and the Finnish Pediatric Research Foundation (to Kolho KL)
Correspondence to: Laura Mäkitalo, MD, PhD, Hospital for Children and Adolescents, Helsinki University Central Hospital, University of Helsinki, PO Box 281, FIN-00029 Helsinki, Finland.
Telephone: +358-50-5418445 Fax: +358-9-47186478
Received: February 21, 2012
Revised: May 9, 2012
Accepted: May 13, 2012
Published online: August 14, 2012

AIM: To investigate matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pouch mucosa of pediatric onset ulcerative colitis (UC).

METHODS: In this cross-sectional study, 28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years (median) after proctocolectomy. Expression of MMPs-3, -7, -8, -9, -12 and -26 and TIMPs-1, -2 and -3 in samples was examined using immunohistochemichal methods, and another biopsy was used to evaluate the grade of histological inflammation. Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion, using a scale marking staining intensity as follows: 0 = less than 20 positive cells; 1 = 20-50 positive cells; 2 = 50-200 positive cells; 3 = over 20 positive cells. Fecal calprotectin and blood inflammatory markers [serum C-reactive protein (CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.

RESULTS: Of the 28 patients with pediatric onset UC, nine had not experienced pouchitis, whereas thirteen reported a single episode, and six had recurrent pouchitis (≥ 4 episodes). At the time of the study, six patients required metronidazole. In all of the others, the most recent episode of pouchitis had occurred over one month earlier, and none were on antibiotics. Only four samples depicted no sign of inflammation, and these were all from patients who had not had pouchitis. Two samples were too small to determine the grade of inflammation, but both had suffered pouchitis, the other recurrent. No sample depicted signs of colonic metaplasia. Most pouch samples showed expression of epithelial (e) and stromal (s) MMP-3 (e, n = 22; s, n = 20), MMP-7 (e, n = 28; s, n = 27), MMP-12 (e, n = 20; s, n =24), TIMP-2 (e, n = 23; s, n = 23) and MMP-3 (e, n = 23; s, n = 28) but MMP-8 (e, n = 0; s, n = 1), MMP-9 (e, n = 0; s, n = 9) and MMP-26 (e, n = 0; s, n = 3) and TIMP-1 (n = 0, both) were lacking. In samples with low grade of inflammatory activity, the epithelial MMP-3 and MMP-7 expression was increased (r = -0.614 and r = -0.472, respectively, P < 0.05 in both). MMPs and TIMPs did not correlate with the markers of inflammation, fecal calprotectin, erythrocyte sedimentation rate, or CRP, with the exception of patients with low fecal calprotectin (< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMP- or TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes. Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP- or TIMP-expression.

CONCLUSION: The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease, but inflammation cannot be classified as a reactivation of the disease.

Keywords: Children, Matrix metalloproteinase 3, Tissue inhibitor of matrix metalloproteinase 3, Matrix metalloproteinase 7, Pouchitis, Ulcerative colitis