Different Profiles of MMP9 Activators in the CSF of MS and CIS Patients (P03.239)

OBJECTIVE: We aimed at assessing MMP-9 activation pathways (EMMPRIN, Cyclophilin A and uPA) in patients with RRMS and clinically isolated syndromes (CIS). BACKGROUND: Metalloproteinases (MMP), particularly MMP-9, have long been implicated in the breakdown of the blood brain barrier, an early and essential step for the development of MS. However, besides the action of the Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), the role of other MMP-9 regulators such as the Extracellular Matrix Metalloproteinase Inducer (EMMPRIN), Cyclophilin A and urokinase Plasminogen Activator (uPA) in MS is still largely unknown. DESIGN/METHODS: We retrospectively identified samples of patients with RRMS, CIS (that remained free from disease progression for 2 years) and controls (with non inflammatory neurological disorders) from the CPMS biobank at our institute and used commercial ELISA assays to assess the CSF concentrations of MMP-9 and its regulators TIMP-1, EMMPRIN, Cyclophilin A and uPA. We also collected demographic and clinical data including, for RRMS and CIS, number of MRI Barkhoff criteria, presence of oligoclonal bands and functional system affected. RESULTS: As previously described, higher MMP-9 and MMP-9/TIMP-1 ratio levels were found in CIS and MS patients, which confirms that these are good candidates to become MS biomarkers. Noticeably, we observed that uPA and EMMPRIN levels are differentially elevated in CIS and MS patients: while uPA levels were elevated in MS cases, EMMPRIN was elevated in CIS. As a result, uPA to EMMPRIN ratio was significantly higher in MS relative to CIS. CONCLUSIONS: In conclusion, the CSF levels of MMP9 and its regulators are useful biomarkers for MS and, after further scrutiny, the uPA to EMMPRIN ratio in the CSF might even become a predictor of CIS conversion, which has to be tested in further studies. Supported by: In part by FEDER European Union funds, through national competitivity factors program (COMPETE), and by national funds through to project PIC/IC/83231/2007. SM is supported by PhD scholarship SFRH/BD/69311/2010 from the Portuguese Science and Technology Foundation. Disclosure: Dr. Cerqueira has received personal compensation for activities with Bayer, Biogen Idec, and Novartis. Dr. Monteiro has nothing to disclose. Dr. Sousa has nothing to disclose. Dr. Cerqueira has received personal compensation for activities with Bayer, Biogen Idec, and Novartis. Dr. Sousa has nothing to disclose. Dr. Marques has nothing to disclose. Dr. Palha has nothing to disclose. Dr. Sousa has nothing to disclose.