JCPyV miR-J1-5p in Urine of Natalizumab-Treated Multiple Sclerosis Patients

The use of Natalizumab in Multiple Sclerosis (MS) can cause the reactivation of the polyomavirus JC (JCPyV); this may result in the development of progressive multifocal leukoencephalopathy (PML), a rare and usually lethal disease. JCPyV infection is highly prevalent in worldwide population, but the detection of anti-JCPyV antibodies is not sufficient to identify JCPyV infection, as PML can develop even in patients with negative JCPyV serology. Better comprehension of the JCPyV biology could allow a better understanding of JCPyV infection and reactivation, possibly reducing the risk of developing PML. Here, we investigated whether JCPyV miR-J1-5p—a miRNA that down-regulates the early phase viral protein T-antigen and promotes viral latency—could be detected and quantified by digital droplet PCR (ddPCR) in urine of 25 Natalizumab-treated MS patients. A 24-month study was designed: baseline, before the first dose of Natalizumab, and after 1 (T1), 12 (T12) and 24 months (T24) of therapy. miR-J1-5p was detected in urine of 7/25 MS patients (28%); detection was possible in three cases at T24, in two cases at T12, in one case at T1 and T12, and in the last case at baseline and T1. Two of these patients were seronegative for JCPyV Ab, and viral DNA was never found in either urine or blood. To note, only in one case miR-J1-5p was detected before initiation of Natalizumab. These results suggest that the measurement of miR-J1-5p in urine, could be a biomarker to monitor JCPyV infection and to better identify the possible risk of developing PML in Natalizumab-treated MS patients.

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Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458514534513 ◽

2014 ◽

Vol 20 (14) ◽

pp. 1851-1859 ◽

Cited By ~ 38

Author(s):

M Muñoz-Culla ◽

H Irizar ◽

T Castillo-Triviño ◽

M Sáenz-Cuesta ◽

L Sepúlveda ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multifocal Leukoencephalopathy ◽

Differential Expression ◽

Expression Pattern ◽

Mirna Expression ◽

Disease Biomarkers ◽

Mirna Expression Pattern ◽

Increased Risk ◽

Relapsing Remitting ◽

Multiple Sclerosis Patients

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.

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Is maraviroc useful in multiple sclerosis patients with natalizumab-related progressive multifocal leukoencephalopathy?

Journal of the Neurological Sciences ◽

10.1016/j.jns.2017.05.018 ◽

2017 ◽

Vol 378 ◽

pp. 233-237 ◽

Cited By ~ 8

Author(s):

Cristina Scarpazza ◽

Luca Prosperini ◽

Chiara R. Mancinelli ◽

Nicola De Rossi ◽

Alessandra Lugaresi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multifocal Leukoencephalopathy ◽

Multiple Sclerosis Patients

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Longitudinal JCV serology in multiple sclerosis patients preceding natalizumab-associated progressive multifocal leukoencephalopathy

Multiple Sclerosis Journal ◽

10.1177/1352458514567728 ◽

2015 ◽

Vol 21 (12) ◽

pp. 1600-1603 ◽

Cited By ~ 17

Author(s):

Anke Vennegoor ◽

Johannis A van Rossum ◽

Chris H Polman ◽

Mike P Wattjes ◽

Joep Killestein

Keyword(s):

Multiple Sclerosis ◽

Risk Factor ◽

Progressive Multifocal Leukoencephalopathy ◽

High Serum ◽

Saturation Level ◽

Antibody Index ◽

John Cunningham Virus ◽

Multiple Sclerosis Patients

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.

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