Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis

Neurology. 1999 Oct 22;53(7):1397-401. doi: 10.1212/wnl.53.7.1397.

Abstract

Objective: To 1) compare monthly serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-type 1 (TIMP-1) in patients with relapsing-remitting MS (RRMS) versus healthy controls and 2) determine the relationship among monthly serum levels of MMP-9 and TIMP-1 and MRI activity.

Background: Activated T-cells and macrophages secrete MMPs that may facilitate their migration across vascular subendothelial basement membranes into the CNS. The serum concentration of MMP-9 is reported to be higher in patients with RRMS than healthy controls.

Methods: Monthly evaluations including gadolinium-enhanced (Gd+) brain MRI and measures of serum MMP-9 and TIMP-1 were performed for up to 15 months in 24 patients with RRMS and for up to 4 months in 10 controls.

Results: Serum MMP-9 but not TIMP-1 levels are elevated in RRMS patients compared to healthy controls (p = 0.025, p = 0.61). In a univariate analysis, high MMP-9 and low TIMP-1 levels precede appearance of new Gd+ lesions (respectively; odds ratio = 3.3, p = 0.008; odds ratio = 2.2, p = 0.086). In a multivariate analysis, in comparison to months when MMP-9 is low and TIMP-1 high, MRI scans obtained the month following high MMP-9 and low TIMP-1 serum concentrations are more likely to report new Gd+ lesions (p = 0.0006, odds ratio = 21.5).

Conclusion: An increase in the activity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor of MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, suggesting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of disease activity in relapsing-remitting MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / pathology
  • Child
  • Female
  • Gadolinium
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / diagnosis*
  • Multivariate Analysis
  • Recurrence
  • Reference Values
  • Regression Analysis
  • Tissue Inhibitor of Metalloproteinase-1 / blood*

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Gadolinium
  • Matrix Metalloproteinase 9