Evidence map›Paper›PMID 34006621›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2021

Exosomes From Subjects With Multiple Sclerosis Express EBV-Derived Proteins and Activate Monocyte-Derived Macrophages.

May F Mrad, Esber S Saba, Layane Nakib, Samia J Khoury

Open access · goldAbstract read
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
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

25 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. A framework for blood biomarker discovery in MS.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
    Review
  3. Review
  4. The Role of Extracellular Vesicles in Epstein-Barr Virus Immunology and Pathogenesis for Possible Diagnostic and Therapeutic Direction.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026
    Review
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  7. In-Depth Characterization of L1CAMInternational journal of molecular sciences · 2025
    Article
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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

4 authors at 1 institution in 1 country.

May F MradFrom the Nehme and Therese Tohme Multiple Sclerosis Center (M.F.M.), Faculty of Medicine, American University of Beirut Medical Center; Department of Experimental Pathology (E.S.S., L.N.), Immunology and Microbiology, Faculty of Medicine, American University of Beirut; and Nehme and Therese Tohme Multiple Sclerosis Center (S.J.K.), and Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Lebanon.ORCID 0000-0003-4379-5862
Esber S SabaFrom the Nehme and Therese Tohme Multiple Sclerosis Center (M.F.M.), Faculty of Medicine, American University of Beirut Medical Center; Department of Experimental Pathology (E.S.S., L.N.), Immunology and Microbiology, Faculty of Medicine, American University of Beirut; and Nehme and Therese Tohme Multiple Sclerosis Center (S.J.K.), and Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Lebanon.ORCID 0000-0003-1525-6394
Layane NakibFrom the Nehme and Therese Tohme Multiple Sclerosis Center (M.F.M.), Faculty of Medicine, American University of Beirut Medical Center; Department of Experimental Pathology (E.S.S., L.N.), Immunology and Microbiology, Faculty of Medicine, American University of Beirut; and Nehme and Therese Tohme Multiple Sclerosis Center (S.J.K.), and Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Lebanon.
Samia J KhouryFrom the Nehme and Therese Tohme Multiple Sclerosis Center (M.F.M.), Faculty of Medicine, American University of Beirut Medical Center; Department of Experimental Pathology (E.S.S., L.N.), Immunology and Microbiology, Faculty of Medicine, American University of Beirut; and Nehme and Therese Tohme Multiple Sclerosis Center (S.J.K.), and Abu Haidar Neuroscience Institute, Faculty of Medicine, American University of Beirut Medical Center, Lebanon. sk88@aub.edu.lb.ORCID 0000-0003-3198-6063
American University of Beirut Medical Center · LB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo investigate in a cross-sectional study the effect of serum-derived exosomes on primary human blood monocyte-derived macrophages (MDMs) comparing exosomes from healthy donors vs patients with relapsing-remitting multiple sclerosis in remission and in relapse and to assess whether the response correlates with exosomal Epstein-Barr virus (EBV) protein expression.

methodsA total of 45 serum-derived exosome preparations were isolated from patients and healthy controls and verified for the expression of exosomal and EBV markers. MDMs were differentiated from monocytes for 7 days and incubated for 24 hours with exosomes, and then, cell supernatants were collected for cytokine measurement by cytometric bead array. Cells were immunophenotyped before and after differentiation.

resultsSerum-derived exosomes of patients with multiple sclerosis (MS) expressed higher levels of EBV proteins than healthy controls. Of interest, expression of EBV nuclear antigen EBNA1 and latent membrane proteins LMP1 and 2A was higher on exosomes derived from patients with active RRMS compared with healthy controls and stable patients. After data normalization, we observed that incubation with EBV(+) exosomes induced CXCL10 and CCL2 secretion by MDMs. MDMs differentiated from patients with active disease were better secretors of CXCL10 and other interferon-γ-inducible chemokines, including CCL2 and CXCL9, than MDMs from healthy and stable MS groups. MDMs from active patients had a higher frequency of a CD14(++) subset that correlated with the secreted CXCL10.

conclusionExosomes expressing EBV proteins correlate with disease activity and induce an inflammatory response in MDMs that is compounded by the origin of the responder cells.

Indexed as

Disease ProgressionAdultCohort StudiesCross-Sectional StudiesEpstein-Barr Virus Nuclear AntigensExosomesFemaleHumansMacrophagesMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingViral Matrix ProteinsEBV-associated membrane antigen, Epstein-Barr virusEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensViral Matrix Proteins

Identifiers

PMID34006621
PMCPMC8130999
OpenAlexW3162283167

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.