Potential relevance of cerebrospinal fluid and serum levels and intrathecal synthesis of active matrix metalloproteinase-2 (MMP-2) as markers of disease remission in patients with multiple sclerosis

Mult Scler. 2009 May;15(5):547-54. doi: 10.1177/1352458509102372. Epub 2009 Mar 24.

Abstract

Background: Little is known about the involvement of matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor TIMP-2 in multiple sclerosis (MS).

Objective: To elucidate the actual implication of MMP-2 and TIMP-2 in MS.

Methods: Cerebrospinal fluid (CSF) and serum levels of active MMP-2 and TIMP-2 were measured by activity assay system and ELISA, respectively, in 67 patients with relapsing-remitting MS (RRMS), categorized according clinical and magnetic resonance imaging (MRI), and in 129 controls.

Results: Cerebrospinal fluid and serum active MMP-2/TIMP-2 ratio mean values and an intrathecal active MMP-2 production were more increased in RRMS than in non-inflammatory conditions (P < 0.001, P < 0.05, and P < 0.0001, respectively) and in MRI inactive than in MRI active RRMS (P < 0.02, P < 0.01 and P < 0.001, respectively). An intrathecal synthesis of active MMP-2 was more frequent in RRMS than in inflammatory disorders (P < 0.01). Serum active MMP-2/TIMP-2 ratio and MS disease duration were positively correlated (P < 0.02).

Conclusion: These findings suggest a potential role for MMP-2 activity in the termination of MS neuroinflammation related to remission of the disease and seem to indicate that serum MMP-2/TIMP-2 ratio may represent a useful biomarker for monitoring MS recovery phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood*
  • Biomarkers / cerebrospinal fluid*
  • Enzyme Activation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Matrix Metalloproteinase 2 / blood*
  • Matrix Metalloproteinase 2 / cerebrospinal fluid*
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / blood*
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Remission Induction
  • Sensitivity and Specificity
  • Tissue Inhibitor of Metalloproteinase-2 / blood
  • Tissue Inhibitor of Metalloproteinase-2 / cerebrospinal fluid

Substances

  • Biomarkers
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2