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

Background - Currently, little is known about the involvement of matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor TIMP-2 in Multiple Sclerosis (MS). Objective - The aim of this study was to elucidate the actual implication of MMP-2 and TIMP-2 in MS pathogenesis and their possible use as biomarkers of the disease. 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 inflammatory and non-inflammatory neurological controls. Results - CSF 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 also 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.