Correlation of MMP-3 and MMP-9 with Crohn's disease activity in children

Dig Dis Sci. 2012 Mar;57(3):706-12. doi: 10.1007/s10620-011-1936-z. Epub 2011 Oct 14.

Abstract

Background: Recently published data indicate that the inflammation in Crohn's disease (CD) may be accompanied by elevated levels of matrix metalloproteinases.

Aims: The goals of the present study were the estimation of MMP-3 and -9 concentrations in sera of children with Crohn's disease, the examination of correlation between the concentrations of MMP-3 and -9 and clinical activity of the disease in the relation to the control group and the evaluation of the utility of MMP-3 and -9 concentration measurements as markers of disease activity.

Methods: Serum concentrations of MMP-3 and -9 were estimated in 82 children (45 CD patients divided into severe, moderate and mild subgroups; 37 controls) and correlated with disease activity estimated by the Pediatric Crohn's Disease Activity Index (PCDAI), CRP, seromucoid and ESR.

Results: Mean MMP-3 concentrations were: 2.49 ng/ml (95% CI: 1.76-3.52) for mild, 16.44 ng/ml (95% CI: 10.34-26.15) for moderate, 5.25 ng/ml (95% CI: 2.73-10.11) for severe CD and 1.95 ng/ml (95% CI: 1.53-2.48) for the control group (differences between all three groups were statistically significant; P < 0.001). Median MMP-9 concentrations were: 2.14 ng/ml (95% CI: 0-8.9) for mild, 14.21 ng/ml (95% CI: 4.53-21.48) for moderate, 42.2 ng/ml (95% CI: 5.74-61.27) for severe CD and 1.3 ng/ml (95% CI: 0.7-2.18) for the control group. MMP-9 concentrations in moderate and severe CD differed from the concentrations in mild CD (P = 0.002) and control group (P = 0.0001). MMP-3 concentration significantly correlated with MMP-9, PCDAI and ESR, while MMP-9 concentration significantly positively correlated with MMP-3, PCDAI, and CRP. Diagnostic utilities of the tests were: MMP-3 accuracy 75%, positive likelihood ratio (LR+) = 4.11 and negative likelihood ratio (LR-) = 0.51, sensitivity 56%, specificity 87%, Youden index 0.43; for MMP-9, accuracy 73%, LR+ = 5.14 and LR- = 0.50, sensitivity 56%, specificity 89%, Youden index 0.45; and for CRP, accuracy 74%, LR+ = 8.56 and LR- = 0.54, sensitivity 49%, specificity 94%, Youden index 0.43.

Conclusions: MMP-9 serum concentration increasing along with the activity of the disease, exhibiting high specificity and correlating well with the indices of inflammation might be of better usefulness in the prediction of CD activity status in children than MMP-3.

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Crohn Disease / blood*
  • Crohn Disease / diagnosis*
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / diagnosis
  • Male
  • Matrix Metalloproteinase 3 / blood*
  • Matrix Metalloproteinase 9 / blood*
  • Predictive Value of Tests
  • Prospective Studies
  • Sensitivity and Specificity
  • Severity of Illness Index*

Substances

  • Biomarkers
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9