Matrix metalloproteinase 9 is decreased in natalizumab‐treated multiple sclerosis patients at risk for progressive multifocal leukoencephalopathy

Abstract

The results from this study suggest that the proangiogenic factor MMP9 may play a role as a biomarker associated with the development of PML in MS patients treated with NTZ. Ann Neurol 2017;82:186-195.

Germline Genetic Risk Variants for Progressive Multifocal Leukoencephalopathy

“…A list of candidate immune function genes was curated from the following main sources: genome-wide study of rare copy number variants in 70 PML cases (Dis cohort) that impact immune function genes (data not shown), genes from the ClinVar database (43) using search terms "immune deficiency" and "immunodeficiency, " IUIS and other immunodeficiency reviews (29,30,(44)(45)(46)(47)(48)(49)(50), type I interferon pathway genes (51)(52)(53)(54)(55)(56)(57)(58), complement pathway genes (59), and JCV or PML linked biology (23,26,33,(60)(61)(62)(63)(64). The full list of 711 unique genes were cross-checked against genes that were found with DV-called variants in the Dis and/or Rep cohorts.…”

Dynamic changes of MMP-9 plasma levels correlate with JCV reactivation and immune activation in natalizumab-treated multiple sclerosis patients

“…have recently reported decreased MMP-9 mRNA levels in PBMC and protein plasma concentrations at baseline in RRMS patients who developed PML, compared to patients who did not experience PML over 5 years of natalizumab treatment. In their study the differences of MMP-9 levels were inconstantly detected after 12 and 24 months of natalizumab treatment in pre-PML and not-PML patients 23 . In that paper, they speculate that reduced levels of molecules involved in BBB disruption, such as MMP-9, could interfere with CD8 + T-lymphocyte immune surveillance mechanisms in the CNS, predisposing MS patients to JCV reactivation and PML development 23 .…”

“…In their study the differences of MMP-9 levels were inconstantly detected after 12 and 24 months of natalizumab treatment in pre-PML and not-PML patients 23 . In that paper, they speculate that reduced levels of molecules involved in BBB disruption, such as MMP-9, could interfere with CD8 + T-lymphocyte immune surveillance mechanisms in the CNS, predisposing MS patients to JCV reactivation and PML development 23 . Our results cannot be directly compared with those obtained by Fissolo et al ., considering that in our cohort we did not observe any case of natalizumab induced PML.…”

“…demonstrated that CSF MMP-9 mean levels were reduced after 12 months of natalizumab treatment in 7 MS patients 22 . Accordingly, other authors showed that serum protein levels of MMP-9 were reduced in RRMS patients after 12 months of natalizumab treatment 23 . While MMP-9 is predominantly upregulated in inflammatory conditions, MMP-2 is constitutively expressed in the brain 24 .…”

CSF/serum matrix metallopeptidase‐9 ratio discriminates neuro Behçet from multiple sclerosis

“…Moreover, the cutoff value of the concentration in serum identify all NBD samples with 100% specificity. In order to take into account the differences between intrathecal and peripheral protein production, we normalized the MMP9 levels with albumin ones, by calculation of “MMP9 Index.”11 MMP9 has been widely investigated in MS12, 13, 14; recently Song et al found that during experimental autoimmune encephalomyelitis (EAE, animal model of MS) MMP9 has a pivotal role at the parenchymal border of CNS, increasing the migration of leukocytes. Furthermore, in EAE MMP9 activity was found regulated by cytokines produced by infiltrating leukocytes and was determinant for the induction of astrocytes chemotactic activity 15.…”