Evidence map›Paper›PMID 41610382›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2026

EBV Dysregulation Is Associated With Immune Imbalance in Multiple Sclerosis: Evidence From Integrated Viral and Host Analyses.

Chiara Meloni, Fabiana Marnetto, Corrado Fagnani, Lucia Benincasa, Diletta Galano, Pankaj Trivedi, Paola Valentino, Serena Martire, Alessia Di Sapio, Antonio Bertolotto and 6 more

Abstract read
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Chiara MeloniDepartment of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Fabiana MarnettoClinical Trial Unit, AO Ordine Mauriziano Hospital, Turin, Italy.
Corrado FagnaniCentre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.ORCID 0000-0001-5771-7772
Lucia BenincasaDepartment of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Diletta GalanoDepartment of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Pankaj TrivediDepartment of Experimental Medicine, Sapienza University, Rome, Italy.
Paola ValentinoDepartment of Neurology and CRESM, University Hospital San Luigi Gonzaga, Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole, Orbassano, Italy.ORCID 0000-0003-3819-9409
Serena MartireDepartment of Neurology and CRESM, University Hospital San Luigi Gonzaga, Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole, Orbassano, Italy.
Alessia Di SapioDepartment of Neurology and CRESM, University Hospital San Luigi Gonzaga, Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole, Orbassano, Italy.ORCID 0000-0002-5575-7567
Antonio BertolottoPercorso Sclerosi Multipla, Koelliker Hospital, Turin, Italy.ORCID 0000-0002-7052-1907
Anna Maria RepiceDepartment of Neuroscience, Drug and Child Health (NEUROFARBA), University of Florence, Italy.
Clara BalleriniDepartment of Experimental and Clinical Medicine (DMSC), University of Florence, Italy; and.
Cristina MancosuDepartment of Medical Science and Public Health, University of Cagliari, MS Centre, Binaghi Hospital, Cagliari, Italy.
Jessica FrauDepartment of Medical Science and Public Health, University of Cagliari, MS Centre, Binaghi Hospital, Cagliari, Italy.
Eleonora CoccoDepartment of Medical Science and Public Health, University of Cagliari, MS Centre, Binaghi Hospital, Cagliari, Italy.ORCID 0000-0002-3878-8820
Caterina VeroniDepartment of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.ORCID 0000-0002-6043-1051

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesEpstein-Barr virus (EBV) infection is a prerequisite for the development of multiple sclerosis (MS), yet whether EBV acts merely as a trigger at disease onset or also contributes to immune dysregulation and disease progression remains unclear. To explore potential mechanisms linking EBV to immune alterations, we performed a comprehensive analysis of EBV markers and immune-related gene expression in peripheral blood samples from therapy-naïve persons with MS (PwMS) and healthy donors (HD) and assessed EBV transcripts in CSF cells to explore compartment-specific viral activity.

methodsPeripheral blood mononuclear cells (PBMCs) and serum from PwMS (n = 77) and HD (n = 40) were analyzed. EBV serology, DNA load, and RNA expression were assessed by ELISA, droplet digital PCR, and preamplified real-time RT-PCR, respectively. EBV RNA was also evaluated in PwMS CSF cells. Gene expression profiling of 47 immune-related genes selected for their relevance to MS was also performed in PBMCs. Data were analyzed using univariate and multivariate statistical approaches also considering demographic, clinical, and radiologic information. Exploratory factor analysis (EFA) was used to identify transcriptional signatures associated with MS.

resultsAnti-EBNA1 IgG titers were higher in PwMS. In addition, EBV RNA and DNA were more frequently detected, and viral load was increased compared with HD. Notably, EBV transcripts associated with latency II/III (LMP1, LMP2A, EBNA1, EBNA3A) and lytic reactivation (BZLF1, gp350/220) were more prevalent in PwMS. Although viral RNA was detected in only 7% of CSF samples, all positive cases showed profiles consistent with viral reactivation. Immune gene expression analysis revealed broad upregulation of cytotoxic effectors, type I interferon pathways, and chemokine signaling in PwMS. EFA identified a significantly different gene signature linking BZLF1 expression with inflammatory genes, type I interferon responses, and chemokines involved in immune cell migration, in PwMS. DISCUSSION: Our findings support the hypothesis that EBV latency disruption and lytic reactivation contribute to immune dysregulation in MS. The association between EBV transcriptional activity and immune gene alterations may uncover potential peripheral biomarkers of EBV-driven pathology. These molecular signatures may provide insights into novel therapeutic avenues and peripheral biomarkers for MS monitoring.

Indexed as

Epstein-Barr Virus InfectionsHerpesvirus 4, HumanMultiple SclerosisAdultFemaleHumansLeukocytes, MononuclearMaleMiddle Aged

Identifiers

PMID41610382
PMCPMC12858333

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