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Cerebrospinal fluid exosomal Epstein-Barr virus microRNAs in multiple sclerosis and effects of disease modifying
Victoria Hyslop Hvalkof1, Malene Bredahl Hansen1, Sahla El Mahdaoui1
1Danish Multiple Sclerosis Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
Abstract:
Epstein-Barr virus (EBV) may be crucial for development of multiple sclerosis (MS). EBV encodes 44 microRNAs (miRNAs) that are found in exosomes. We investigated EBV miRNAs in cerebrospinal fluid (CSF) exosomes in 50 newly diagnosed people with relapsing-remitting MS (pwRRMS), 24 with clinically isolated syndromes (CIS), 45 symptomatic controls (SC), 15 anti-CD20 antibody-treated 24 natalizumab (NTZ)-treated pwRRMS. miRNAs were measured by quantitative PCR. Plasma anti-EBNA1 antibody and various CSF biomarkers were measured by immunoassays. ebv-miR-BART13-5p and ebv-miR-BART19-3p were reliably measured. ebv-miR-BART19-3p was lower in pwRRMS and correlated with disease severity. In NTZ-treated pwRRMS, ebv-miR-BART19-3p was higher, correlated with treatment duration, and was associated with soluble B-cell maturation antigen, CD27, and zonula occludens-1. No differences were observed in anti-CD20 antibody-treated pwRRMS. These findings may reflect the presence of more exosome recipient cells in pwRRMS, resulting in fewer exosomes as they become internalized in recipient cells along with their EBV miRNA cargo.
Insights
Epstein-Barr virus (EBV) microRNAs (miRNAs) in cerebrospinal fluid exosomes may indicate multiple sclerosis (MS) activity. Lower levels of a specific EBV miRNA correlated with MS severity and treatment response.
Area of Science:
- Neurovirology
- Immunology
- Molecular Biology
Background:
- Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) pathogenesis.
- EBV encodes microRNAs (miRNAs) packaged within exosomes, which can mediate intercellular communication.
Purpose of the Study:
- To investigate the presence and levels of EBV miRNAs in cerebrospinal fluid (CSF) exosomes from individuals with MS and related conditions.
- To explore the correlation between EBV miRNA levels and MS disease characteristics, severity, and treatment status.
Main Methods:
- Quantitative PCR was used to measure EBV miRNAs in CSF exosomes from newly diagnosed relapsing-remitting MS (pwRRMS), clinically isolated syndromes (CIS), symptomatic controls (SC), and patients treated with anti-CD20 antibodies or natalizumab (NTZ).
- Immunoassays were employed to measure plasma anti-EBNA1 antibodies and CSF biomarkers.
Main Results:
- The EBV miRNAs ebv-miR-BART13-5p and ebv-miR-BART19-3p were reliably quantified.
- Lower levels of ebv-miR-BART19-3p were observed in pwRRMS and correlated with disease severity.
- In NTZ-treated pwRRMS, ebv-miR-BART19-3p levels were higher, correlated with treatment duration, and associated with specific biomarkers (sCD27, CD27, ZO-1).
- No significant differences in EBV miRNA levels were found in anti-CD20 antibody-treated pwRRMS.
Conclusions:
- EBV miRNA levels in CSF exosomes may serve as potential biomarkers for MS activity and progression.
- The observed changes in ebv-miR-BART19-3p levels might reflect alterations in exosome uptake by recipient cells in pwRRMS.
- Differential responses in EBV miRNA levels between NTZ and anti-CD20 treatments warrant further investigation.
