MMP-9 activity dynamics in relapsing-remitting multiple sclerosis patients under natalizumab treatment and their relationship to T-lymphocyte phenotypes

Natalizumab (NTZ) increases the risk of developing progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). The aim of the study was to describe the modifications of matrix metalloproteinase (MMP)-9 activity during NTZ treatment in parallel with T-lymphocyte phenotypic alterations. Thirty-nine relapsing remitting multiple sclerosis (RRMS) patients under NTZ treatment were included in the study. In all plasma samples stratified according to NTZ infusion number (N0:0, N12:1-12, N24:13-24, N36:25-36 infusions of NTZ) MMP-9 activity, T-lymphocyte phenotype and JCV-DNA presence were evaluated. MMP-9 activity increased in the N24 group. CD8 immune activation, and CD4 and CD8 immunosenescence levels were positively correlated to MMP-9 activity values. CD4 and CD8 effector percentages and MMP-9 activity values were positive correlated. Finally, a negative correlation between CD8 naïve percentages and MMP-9 activity values was found. Stratifying plasma samples according to JCV-DNA detection, plasma MMP-9 activity was increased in JCV-DNA+ in comparison with JCV-DNA- samples. MMP-9 activity increased during the 2nd year of NYZ treatment, when PML risk starts to increase. Furthermore MMP-9 activity was higher in patients with detectable JCV-DNA in plasma samples and positively correlated with T-lymphocyte activation markers and immunosenescence. These results suggest a potential pathogenic role of MMP-9 in the development of PML during NTZ treatment.

Maria Antonella Zingaropoli
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