Evidence map›Paper›PMID 40970118›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Intrathecally expanded GZMK+/GZMH+ CD8 T cells targeting EBV antigens may reduce severity of Multiple Sclerosis.

Shinji Ashida, Peter Kosa, Francisco Otaizo-Carrasquero, Dan Sturdevant, Amirhossein Shamsaddini, Yongmei Zhao, Jyoti Shetty, Craig Martens, Jeffrey I Cohen, Bibiana Bielekova

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. 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

10 authors.

Shinji AshidaNeuroimmunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Peter KosaNeuroimmunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Francisco Otaizo-CarrasqueroGenomic Research Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Dan SturdevantGenomic Research Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Amirhossein ShamsaddiniGenomic Research Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Yongmei ZhaoSequencing Facility Bioinformatics Group, Advanced Biomedical and Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Jyoti ShettySequencing Facility Bioinformatics Group, Advanced Biomedical and Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Craig MartensGenomic Research Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jeffrey I CohenMedical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Bibiana BielekovaNeuroimmunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-0959-9430

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Combining cerebrospinal fluid B cell receptor and T cell receptor repertoire analysis with transcriptional/ flow cytometry cellular profiles in hundreds of deeply-phenotyped people with Multiple Sclerosis (pwMS) and controls, we identified intrathecal expansion of anti-viral, cytotoxic, granzymes H/K (GZMH+/GZMK+) double positive (DP) CD8+ T cells that recognize EBV epitopes in pwMS. DP CD8+ T cells are activated and expanded by, and kill autologous, EBV-infected CSF B cell lines in-vitro. Correlations of surrogate transcriptional profiles with clinical and imaging outcomes infer a beneficial role for EBV-targeting DP CD8+ T cells, as untreated pwMS with proportionally higher DP CD8+ T cells to intrathecal B cells accumulate neurological disability slower. MS therapies also increase ratios of beneficial CD8+ T cell responses to intrathecal B cells, consistent with their ability to inhibit disability progression. This study provides indirect evidence that intrathecal EBV infection participates in disability accumulation in pwMS.

Identifiers

PMID40970118
PMCPMC12443058

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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.