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-g (MMP-9) and tissue inhibitor of MMP-type 1 (TIMP-1) in patients with relap sing-remitting MS (RRMS) versus healthy controls and 2) determine the relat ionship among monthly serum levels of MMP-9 and TIMP-1 and MRI activity. Ba ckground: Activated T-cells and macrophages secrete MMPs that may facilitat e their migration across vascular subendothelial basement membranes into th e CNS. The serum concentration of MMP-9 is reported to be higher in patient s with RRMS than healthy controls. Methods: Monthly evaluations including g adolinium-enhanced (Gd+) brain MRI and measures of serum MMP-9 and TIMP-1 w ere 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 eleva ted 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 ac tivity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor o f MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, sugges ting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of dise ase activity in relapsing-remitting MS.