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Published on: February 12, 2018
JCPyV microRNA in plasma inversely correlates with JCPyV seropositivity among long-term natalizumab-treated
Pabitra Basnyat1, Elina Virtanen2, Irina Elovaara3,4
1Neuroimmunology Unit, School of Medicine, University of Tampere, Tampere, Finland. pabitra.basnyat@uta.fi.
Abstract:
Sensitive biomarkers are needed to better manage multiple sclerosis (MS) patients for natalizumab (NTZ)-associated risk of progressive multifocal leukoencephalopathy (PML). A currently used risk stratification algorithm, mainly based on JC polyomavirus (JCPyV) serology, has not led to a reduction of PML incidence. Therefore, this study was designed to evaluate the presence and prevalence of JCPyV miRNAs in plasma of NTZ-treated MS patients, and to explore their biomarker potential for NTZ-associated PML risk assessment. Altogether, 102 plasma samples from 49 NTZ-treated and 28 interferon-beta (IFN-β)-treated relapsing-remitting MS patients, and 25 healthy controls (HCs) were analyzed for jcv-miR-J1-5p (5p miRNA) and jcv-miR-J1-3p (3p miRNA) expression. The overall detection rate of 5p miRNA was 84% (41/49) among NTZ-treated patients, 75% (21/28) among IFN-β-treated patients, and 92% (23/25) in HCs. Relative 5p miRNA expression levels were lower in NTZ-treated patients as compared to patients treated with IFN-β (p = 0.027) but not to HCs. Moreover, 5p miRNA expression inversely correlated with anti-JCPyV antibody index among JCPyV seropositive long-term NTZ-treated patients (r = -0.756; p = 0.002). The overall detection rate of 3p miRNA was low. Our results suggest that JCPyV miRNA in plasma may be linked to the reactivation of persistent JCPyV, to enhanced virus replication, and eventually to the risk of developing PML among NTZ-treated MS patients. However, further study is warranted in a larger data set including samples from PML patients to confirm the clinical relevance of JCPyV miRNA as a sign of/in viral reactivation, and to identify its potential to predict developing PML risk.
Insights
JC polyomavirus (JCPyV) microRNAs (miRNAs) in plasma may indicate reactivation in multiple sclerosis (MS) patients treated with natalizumab (NTZ). Lower 5p miRNA levels correlate with higher JCPyV antibody index, suggesting potential for PML risk assessment.
Area of Science:
- Neuroimmunology
- Virology
- Biomarker Discovery
Background:
- Natalizumab (NTZ) treatment for multiple sclerosis (MS) carries a risk of progressive multifocal leukoencephalopathy (PML).
- Current JC polyomavirus (JCPyV) serology-based risk stratification has limitations in reducing PML incidence.
- Sensitive biomarkers are crucial for managing NTZ-associated PML risk.
Purpose of the Study:
- To evaluate the presence and prevalence of JCPyV microRNAs (miRNAs) in plasma of NTZ-treated MS patients.
- To explore the potential of JCPyV miRNAs as biomarkers for NTZ-associated PML risk.
- To investigate the relationship between JCPyV miRNA expression and JCPyV antibody index.
Main Methods:
- Analysis of plasma samples from NTZ-treated MS patients, interferon-beta (IFN-β)-treated MS patients, and healthy controls (HCs).
- Quantification of jcv-miR-J1-5p (5p miRNA) and jcv-miR-J1-3p (3p miRNA) expression.
- Correlation analysis between 5p miRNA levels and anti-JCPyV antibody index.
Main Results:
- The 5p miRNA was detected in 84% of NTZ-treated patients, 75% of IFN-β-treated patients, and 92% of HCs.
- Relative 5p miRNA expression was lower in NTZ-treated patients compared to IFN-β-treated patients (p=0.027).
- A significant inverse correlation was observed between 5p miRNA expression and anti-JCPyV antibody index in JCPyV seropositive NTZ-treated patients (r=-0.756; p=0.002).
Conclusions:
- JCPyV miRNAs in plasma may be associated with JCPyV reactivation and enhanced viral replication in NTZ-treated MS patients.
- These findings suggest a potential role for JCPyV miRNAs in assessing PML risk.
- Further studies with larger datasets, including PML patients, are needed to confirm clinical relevance and predictive potential.
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