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Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment

Department of Medical and Occupational Sciences, University of Foggia, Foggia, Italy, avolio{at}neurol.uniba.it

M Filippi

Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy

C Tortorella

Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

M A Rocca

Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy

M Ruggieri

Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

F Agosta

Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy

V Tomassini

Department of Neurological Sciences, University La Sapienza, Rome, Italy

C Pozzilli

Department of Neurological Sciences, University La Sapienza, Rome, Italy

S Stecchi

Neurology Unit, A.U.S.L. Bologna, Bologna, Italy

P Giaquinto

Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

P Livrea

Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

M Trojano

Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

Matrix metalloproteinase-9 (MMP-9) is involved in blood-brain barrier (BBB) disruption in active multiple sclerosis (MS), while MMP-2 seems to be associated with the chronic progressive phase of the disease. Recombinant interferon beta-1a (rIFNß-1a) is effective in restoring the BBB. We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNß-1a. Twenty-one relapsing-remitting (RR) MS patients underwent longitudinally simultaneous blood withdrawals and MRI (before and after standard dose (SD) and triple dose (TD) of gadolinium (Gd)) examinations before and during 48 weeks of rIFNß-1a (Rebif® 22 mcg three times a week) treatment. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured, MMP-9 to TIMP-1 and MMP-2 to TIMP-2 ratios were calculated and the numbers of Gd-SD, Gd-TD, new-Gd-SD, new-Gd-TD and new-T2 lesions counted. Serum MMP-9/TIMP-1 ratio (P< 0.0001), as well as the numbers of ‘active’ lesions (P ranging from 0.0004 to 0.005) decreased during treatment. Moreover, serum MMP-9/TIMP-1 ratio proved to be a good positive predictor (estimate= 0.85; P> 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TIMP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS.

Key Words: gadolinium triple dose • interferon beta • MMP-9/TIMP-1 • MMP-2/TIMP-2 • MRI • multiple sclerosis

Multiple Sclerosis, Vol. 11, No. 4, 441-446 (2005)
DOI: 10.1191/1352458505ms1193oa


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