Evidence map›Paper›PMID 41919465›Full record

ReviewImmunological reviews2026

Why Is MS a More Frequent Complication of EBV Infection in Females?

Shannon E Dunn, Nuria Alvarez-Sanchez, Lawrence Steinman

Abstract readReview
In one paragraph

Review in Immunological reviews, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Shannon E DunnSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0002-6878-0563
Nuria Alvarez-SanchezCell and Systems Biology, The Hospital for Sick Children (SickKids) Research Institute, Toronto, Ontario, Canada.
Lawrence SteinmanNeurology and Neurological Sciences, Stanford University, Stanford, California, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple sclerosis (MS) is a T helper (Th) cell-mediated disease that targets central nervous system (CNS) white matter. This disease affects three times more females than males. For many years, the etiology of MS was not well understood and the exact nature of the autoimmune reaction was speculative. It has now become clear that MS is a rare complication of Epstein-Barr Virus (EBV) infection and that the virus induces an EBV nuclear antigen (EBNA-1)-specific T and B cell response that is cross-reactive against a number of CNS antigens including Glial cell-associated membrane protein (GlialCAM), Anoctamin-2 (Ano-2), myelin basic protein (MBP), and alpha-B-crystallin (CRYAB). Recent studies have clarified the involvement of the major human leukocyte antigen (HLA) MS risk haplotype, HLA-DR15, in sustaining autoreactive T cell responses and its interaction with EBV. Here, we overview this literature through the lens that MS is a disease that affects females more than males. We describe how EBV seroprevalence and the incidence of infectious mononucleosis are greater in females during the early teen years, a period of increased MS susceptibility. We overview how females with MS develop greater levels of EBNA-1-cross-reactive autoantibodies and show greater myelin-specific T helper 1 (Th1) cells in peripheral blood. Finally, we provide evidence that EBV-infected B cells may achieve a greater state of latency in females and discuss how this may perpetuate CNS autoimmunity. At the same time, our literature search identified many missed opportunities to learn about sex differences in MS. Our hope is that this review will motivate researchers in the future to disaggregate data by sex to accelerate discoveries in this disease.

Indexed as

Epstein-Barr Virus InfectionsHerpesvirus 4, HumanMultiple SclerosisAnimalsB-LymphocytesEpstein-Barr Virus Nuclear AntigensFemaleHumansMaleSex FactorsEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensEpstein–Barr virusHLA‐DR15infectious mononucleosismolecular mimicrymultiple sclerosissex differenceT helper 1 responses

Identifiers

PMID41919465
PMCPMC13040526

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.