Published online Jun 7, 2013. doi: 10.3748/wjg.v19.i21.3272
Revised: April 15, 2013
Accepted: April 18, 2013
Published online: June 7, 2013
AIM: To investigate whether matrix metalloproteinases-9 (MMP-9) or trypsinogens could serve as histological markers for an aggressive disease course in pediatric ulcerative colitis (UC).
METHODS: We identified 24 patients with pediatric onset (≤ 16 years) UC who had undergone surgery during childhood/adolescence a median of 2.1 years (range 0.1-7.4 years) after the diagnosis (between 1990 and 2008) in Children’s Hospital, Helsinki, Finland. We also identified 27 conservatively treated UC patients and matched them based on their age at the time of diagnosis and follow-up at a median of 6 years (range 3-11 years) to serve as disease controls. Twenty children for whom inflammatory bowel disease (IBD) had been excluded as a result of endoscopy served as non-IBD controls. Colon biopsies taken by diagnostic endoscopy before the onset of therapy were stained using immunohistochemistry to study the expression of MMP-9, trypsinogen-1 (Tryp-1), Tryp-2, and a trypsin inhibitor (TATI). The profiles of these proteases and inhibitor at diagnosis were compared between the surgery group, the conservatively treated UC patients and the non-IBD controls.
RESULTS: The proportions of Tryp-1 and Tryp-2 positive samples in the colon epithelium and in the inflammatory cells of the colon stroma were comparable between the studied groups at diagnosis. Interestingly, the immunopositivity of Tryp-1 (median 1; range 0-3) was significantly lower in the epithelium of the colon in the pediatric UC patients undergoing surgery when compared to that of the conservatively treated UC patients (median 2; range 0-3; P = 0.03) and non-IBD controls (median 2; range 0-3; P = 0.04). For Tryp-2, there was no such difference. In the inflammatory cells of the colon stroma, the immunopositivities of Tryp-1 and Tryp-2 were comparable between the studied groups at diagnosis. Also, the proportion of samples positive for TATI, as well as the immunopositivity, was comparable between the studied groups in the colon epithelium. In the stromal inflammatory cells of the colon, TATI was not detected. In UC patients, there were significantly more MMP-9 positive samples and a higher immunopositivity in the stromal inflammatory cells of the colon when compared to the samples from the non-IBD patients (P = 0.006 and P = 0.002, respectively); the immunopositivity correlated with the histological grade of inflammation (95%CI: 0.22-0.62; P = 0.0002), but not with the other markers of active disease. There were no differences in the immunopositivity or in the proportions of MMP-9 positive samples when examined by epithelial staining. The staining profiles in the ileal biopsies were comparable between the studied groups for all of the studied markers.
CONCLUSION: For pediatric UC patients who require surgery, the immunopositivity of Tryp-1 at diagnosis is lower when compared to that of patients with a more benign disease course.
Core tip: The risk factors for aggressive pediatric ulcerative colitis (UC) were studied in 24 patients who had undergone surgery by staining diagnostic tissue samples for matrix metalloproteinase-9 and trypsinogen-1 (Tryp-1) and Tryp-2, as well as a trypsin inhibitor. In the UC group, there were significantly more samples that were matrix metalloproteinase-9 positive in comparison to the samples from non-inflammatory bowel disease patients. UC patients undergoing colectomy showed lower immunopositivity of Tryp-1 in the colon epithelium in their diagnostic biopsies when compared to that of conservatively treated patients and non-inflammatory bowel disease patients. The discovery of a low trypsinogen level at diagnosis warrants further study.