title: Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: UCSF/Mt. Zion Multiple Sclerosis Center, San Francisco, CA 94115, USA.
authors.forename: E
authors.initials: E
authors.lastname: Waubant
authors.forename: D E
authors.initials: DE
authors.lastname: Goodkin
authors.forename: L
authors.initials: L
authors.lastname: Gee
authors.forename: P
authors.initials: P
authors.lastname: Bacchetti
authors.forename: R
authors.initials: R
authors.lastname: Sloan
authors.forename: T
authors.initials: T
authors.lastname: Stewart
authors.forename: P B
authors.initials: PB
authors.lastname: Andersson
authors.forename: G
authors.initials: G
authors.lastname: Stabler
authors.forename: K
authors.initials: K
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D002648:Child; D005260:Female; D005682:Gadolinium; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis*; D015999:Multivariate Analysis; D012008:Recurrence; D012016:Reference Values; D012044:Regression Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D005682:Gadolinium; D020780:Matrix Metalloproteinase 9