title: Low trypsinogen-1 expression in pediatric ulcerative colitis patients who undergo surgery.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Children's Hospital, University of Helsinki, FIN-00029 HUS, Helsinki, Finland. maija.piekkala@helsinki.fi
authors.forename: Maija
authors.initials: M
authors.lastname: Piekkala
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
authors.forename: Maarit
authors.initials: M
authors.lastname: Tanskanen
authors.forename: Risto
authors.initials: R
authors.lastname: Rintala
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000201:enzymology* / Q000601:surgery*; D003106:Colon / Q000201:enzymology* / Q000601:surgery*; D003113:Colonoscopy; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D014357:Trypsin / Q000032:analysis*; D014361:Trypsin Inhibitors / Q000032:analysis; D014362:Trypsinogen / Q000032:analysis
chemical_list: D015415:Biomarkers; D014361:Trypsin Inhibitors; C064831:PRSS2 protein, human; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Children; Inflammatory bowel disease; Matrix metalloproteinase-9 resection; Trypsin inhibitor; Ulcerative colitis