Abstract Details

Title Different Profiles of MMP9 Activators in the CSF of MS and CIS Patients

Topic MS and Related Diseases

Presentation(s) P03 - (-)

Poster/Presentation
Number 239

Objective

Background 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 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 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 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.

Authors/Disclosures
Joao J. Cerqueira, MD, PhD PRESENTER	Dr. Cerqueira has received personal compensation for serving as an employee of João José Cerqueira Unipessoal Lda. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIOGEN. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Cerqueira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. The institution of Dr. Cerqueira has received research support from Biogen.
	No disclosure on file
Ana Sousa (Centro Hospitalar do Porto)	No disclosure on file
	No disclosure on file
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