Matrix metalloproteinases (MMPs) have recently been implicated in the pathogenesis of multiple sclerosis. Their suggested role includes the disruption of the blood-brain barrier, immune cell transmigration into the central nervous system, and myelin degradation. The present study characterized the mRNA level of a wide spectrum of MMPs and tissue inhibitors of metalloproteinases (TIMPs) expressed by peripheral blood leukocytes from relapsing-remitting (n = 16) and secondary-progressive (n = 12) multiple sclerosis patients. The expression of the same MMPs and TIMPs was evaluated also in a prospective 12-month follow-up of 6 patients randomly chosen from each of the 2 groups during interferon beta-1a treatment. Reverse transcription-polymerase chain reaction assessment demonstrated elevated levels of MT1-MMP and MMP-7 mRNA levels in both groups of patients, and no significant differences in MMP-9 levels, compared with healthy controls. Divergent expression of MMP-2 between relapsing-remitting and secondary-progressive patients compared with controls was observed. Interferon-beta treatment was associated with significant suppression of MMP-9 and MMP-7 mRNA in relapsing-remitting patients, though no significant changes were observed in the secondary-progressive group. These results contribute to the understanding of the IFN-beta-mediated immunomodulatory and therapeutic effects in multiple sclerosis patients and also support evidence for distinct immune mechanism(s) underlying relapsing-remitting versus secondary-progressive multiple sclerosis. The study also suggests that MMPs may be considered as potential biomarkers for response to treatment as well as targets for immunotherapy in multiple sclerosis.
The need to ensure an accurate diagnosis and proper treatment for multiple sclerosis patients, considering the various clinical and immunopathological subtypes of the disease, requires the identification of biomarkers that measure disease activity and predict the course of disease development in individual patients. Moreover, the identification of effective indicators will lead not only to optimized patient treatment but also to the development of better tools for evaluating clinical trials. Recent studies focusing on the identification of possible immunological markers in multiple sclerosis will be reviewed.
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