Metalloproteinase 9 as a biomarker of progressive multifocal leukoencephalopathy development in multiple sclerosis patients receiving natalizumab

2017 ◽  
Vol 82 (4) ◽  
pp. 647-647
Author(s):  
Hamid Zahednasab ◽  
Mohammad Hossein Harirchian ◽  
Sajad Karampoor ◽  
Hossein Keyvani
2014 ◽  
Vol 20 (14) ◽  
pp. 1851-1859 ◽  
Author(s):  
M Muñoz-Culla ◽  
H Irizar ◽  
T Castillo-Triviño ◽  
M Sáenz-Cuesta ◽  
L Sepúlveda ◽  
...  

Background: Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability; however, it has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). The differential expression of microRNA (miRNA), the small non-coding RNAs that regulate gene expression, in natalizumab-treated patients has been reported and miRNA have also been described as good candidates for disease biomarkers. Objective: To characterize the effect of natalizumab therapy on the miRNA expression pattern and to search for miRNAs that can predict PML on an individual basis. Methods: The expression of 754 microRNAs was measured in blood samples from 19 relapsing–remitting MS patients at three time points during natalizumab therapy, using TaqMan OpenArray panels. Two patients included in this study developed PML after more than 2 years of therapy. Results: We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy (t6). Furthermore, we observed a differential expression of another three miRNAs (miR-320, miR-320b and miR-629) between the PML and non-PML groups after 12 months of treatment (t12); and a positive correlation was found between therapy time and the expression of miR-320. Conclusions: Natalizumab modified the expression levels of three miRNAs after a 6-month treatment. We suggest miR-320, miR-320b and miR-629 as possible biomarkers for individual PML risk assessment.


2017 ◽  
Vol 378 ◽  
pp. 233-237 ◽  
Author(s):  
Cristina Scarpazza ◽  
Luca Prosperini ◽  
Chiara R. Mancinelli ◽  
Nicola De Rossi ◽  
Alessandra Lugaresi ◽  
...  

2015 ◽  
Vol 21 (12) ◽  
pp. 1600-1603 ◽  
Author(s):  
Anke Vennegoor ◽  
Johannis A van Rossum ◽  
Chris H Polman ◽  
Mike P Wattjes ◽  
Joep Killestein

The presence of anti-John Cunningham Virus (JCV) antibodies is a risk factor for the development of progressive multifocal leukoencephalopathy (PML) in MS patients treated with natalizumab. It has been suggested that an increase in serum anti-JCV antibody index precedes the development of PML. We here describe extensive longitudinal serum anti-JCV antibody indexes of four MS patients who developed PML. Anti-JCV antibodies were measured using the STRATIFY JCV™DxSelect™ test. All four patients had rather stable high anti-JCV antibody indexes in all samples obtained before developing PML. Possibly caused by reaching the saturation level of the assay, no increase in anti-JCV antibody indexes was seen just before the diagnosis of PML. This study confirms that high serum anti-JCV antibody indexes precede natalizumab-associated PML.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandro Trentini ◽  
Massimiliano Castellazzi ◽  
Carlo Cervellati ◽  
Maria Cristina Manfrinato ◽  
Carmine Tamborino ◽  
...  

Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p<0.001andp<0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p<0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r=0.3,p<0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process.


2019 ◽  
Vol 85 (4) ◽  
pp. 606-610 ◽  
Author(s):  
Gloria Dalla Costa ◽  
Vittorio Martinelli ◽  
Lucia Moiola ◽  
Francesca Sangalli ◽  
Bruno Colombo ◽  
...  

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