ERMES: EMILIA ROMAGNA MULTIPLE SCLEROSIS. REGIONAL NETWORK FOR IMPLEMENTING A BIOLOGICAL BANK TO IDENTIFY MARKERS OF DISEASE ACTIVITY RELATED TO CLINICAL VARIABLES Identification of a TIMP-1-resistant active MMP-9 in serum of Multiple Sclerosis patients

Objectives: Gelatinases (MMP-9 and MMP-2) have emerged as potential biomarkers for monitoring Multiple Sclerosis (MS) disease activity (1, 2). Recently, Bellini et al. (3) identified in serum the presence of a TIMP-resistant MMP-9 isoform, that escaping the physiological regulation by its inhibitor could be detrimental in inflammatory conditions. The objective was to investigate serum concentrations of TIMP-resistant MMP-9 in MS patients and inflammatory (OIND) and non-inflammatory (NIND) controls to elucidate its potential relevance as biomarker in the disease. Methods: The presence of TIMP-resistant MMP-9 was evaluated in serum samples from 48 relapsing-remitting (RR) MS patients (active (N=22) and stable (N= 26)), in 30 OIND patients and in 28 NIND patients by an activity assay system adapted by us (3). Results: There were no differences in serum levels of TIMP-resistant active MMP-9 among RRMS OIND and NIND nor between patients categorized on the basis of MRI disease activity. However, the relative amount of TIMP-resistant MMP-9 activity was lower in active RRMS than in OIND (p< 0.05) and MRI stable RRMS patients (p< 0.01). Discussion: Our preliminary results suggest that TIMP-resistant MMP-9 isoform that escapes from the physiological control is more represented in MS than in other inflammatory conditions and might be related to the remission of the disease. These findings indicate that this active MMP-9 isoform could be implicated in processes regulating proteolytic activity in MS. Conclusion: The determination of TIMP-resistant MMP-9 levels might be useful to discriminate between RRMS patients in active phase of disease and inflammatory controls as well as to monitor disease activity.