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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

Neuroradiology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy henryfai{at}tin.it

M Castellazzi

Section of Neurology, Department of Medical and Surgical Sciences of the Communication and Behaviour, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

C Tamborino

Section of Neurology, Department of Medical and Surgical Sciences of the Communication and Behaviour, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

A Trentini

Section of Biochemistry and Clinical Biochemistry, Department of Biochemistry and Molecular Biology, University of Ferrara, via Luigi Borsari 46, Ferrara I-44100, Italy

MC Manfrinato

Section of Biochemistry and Clinical Biochemistry, Department of Biochemistry and Molecular Biology, University of Ferrara, via Luigi Borsari 46, Ferrara I-44100, Italy

E Baldi

Neurology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

MR Tola

Neurology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

F Dallocchio

Section of Biochemistry and Clinical Biochemistry, Department of Biochemistry and Molecular Biology, University of Ferrara, via Luigi Borsari 46, Ferrara I-44100, Italy

E Granieri

Neuroradiology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara I-44100, Italy

T Bellini

Section of Biochemistry and Clinical Biochemistry, Department of Biochemistry and Molecular Biology, University of Ferrara, via Luigi Borsari 46, Ferrara I-44100, Italy

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.

Key Words: cerebrospinal fluid • intrathecal synthesis • MMP-2 • multiple sclerosis • TIMP-2

This version was published on May 1, 2009

Multiple Sclerosis, Vol. 15, No. 5, 547-554 (2009)
DOI: 10.1177/1352458509102372


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