ArticleFrontiers in immunology2024
In-depth analysis of serum antibodies against Epstein-Barr virus lifecycle proteins, and EBNA1, ANO2, GlialCAM and CRYAB peptides in patients with multiple sclerosis.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Elusive B Cell Antigen in Multiple Sclerosis: Time to Rethink CNS B Cell Functions.International journal of molecular sciences · 2025Pooled it
- EBNA1Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Epstein-Barr Virus and Multiple Sclerosis: A Narrative Review on Prevention and the Concept of an Infection-Driven Disease.Biomedicines · 2026Review
- Extensive peripheral immunoglobulin repertoire analyses in people with multiple sclerosis reveal disease-specific signatures and distinct treatment effects of disease modifying drugs.Journal of neuroinflammation · 2026Article
- EBV Dysregulation Is Associated With Immune Imbalance in Multiple Sclerosis: Evidence From Integrated Viral and Host Analyses.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Toward a global research agenda for preventing multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026Article
- Analytical validation of a multiplexed peptide microarray for multi-antigen Epstein-Barr virus serological profiling across diverse clinical specimens.Frontiers in immunology · 2026Article
- HHV-6 and EBV reactivation in relapsing remitting multiple sclerosis: Disability, progression, and inflammation links.iScience · 2025Article
- Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis.International journal of molecular sciences · 2025Observational
- Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: A strong association between multiple sclerosis (MS) and Epstein-Barr virus (EBV) has been established but the exact role of EBV in MS remains controversial. Recently, molecular mimicry between EBNA1 and specific GlialCAM, CRYAB and ANO2 peptides has been suggested as a possible pathophysiological mechanism. The aim of this study was to analyse anti-EBV antibodies in MS patients against (I) EBV lifecycle proteins, (II) putative cross-reactive peptides, and (III) during treatment. Methods: In this retrospective cross-sectional study, 258 serum samples were included consisting of EBV-negative (n = 25) and EBV-positive (n = 36) controls, 192 MS samples including untreated relapsing-remitting MS (RRMS) with and without relapses, secondary progressive MS (SPMS) and primary progressive MS (PPMS) patients, and 106 patients on 8 different treatment regimens. IgG and IgM antibody titers against EBV docking/fusion proteins (gp350, gh/gp42, gh/gL/gp42), immediate early antigen (BZLF1), early antigens (EA p85, EA P138, EA P54), capsid antigens (VCA P18, VCA P23, VCA gp125) and late antigens (EBNA1) were measured. Specific EBNA1 and GlialCAM, CRYAB and ANO2 peptides were synthesized and also incorporated in our custom magnetic bead based multiplex assay. Results: We observed significantly elevated IgG antibody titers in EBV-positive controls, RRMS with and without relapse, SPMS and PPMS patients for all lifecycle antigens except for several early antigens when compared to EBV-negative controls. Significantly higher IgG antibody titers were observed in RRMS patients for fusion proteins and EBNA1 peptides when compared to EBV-positive controls. An MS specific response was observed for ANO2 but not for GlialCAM or CRYAB. No significant treatment effects or a specific IgM response were detectable. Conclusion: The MS-specific, differential antibody response to EBV antigens confirms an altered immunological response to EBV in MS patients. EBV reactivation does not appear to play an important role in MS pathogenesis and no differential antibody signatures were observed between MS disease phases. The MS-specific anti-ANO2 antibody response suggests a potential role for EBNA1 as an antigenic driver, although the exact role of anti-ANO2 antibodies needs to be determined. The precise pathophysiological role of EBV in MS remains uncertain and requires further investigation.
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