Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis.
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.
Waubant
E
E
UCSF/Mt. Zion Multiple Sclerosis Center, San Francisco, CA 94115, USA.
Goodkin
D E
DE
Gee
L
L
Bacchetti
P
P
Sloan
R
R
Stewart
T
T
Andersson
P B
PB
Stabler
G
G
Miller
K
K
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*
D019715:Tissue Inhibitor of Metalloproteinase-1; D005682:Gadolinium; D020780:Matrix Metalloproteinase 9