Evidence map›Paper›PMID 33953718›Full record

Observational studyFrontiers in immunology2021

Innate Immune Modulation Induced by EBV Lytic Infection Promotes Endothelial Cell Inflammation and Vascular Injury in Scleroderma.

Antonella Farina, Edoardo Rosato, Michael York, Benjamin E Gewurz, Maria Trojanowska, Giuseppina Alessandra Farina

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 3 pooled it
–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

21 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  16. Endothelial Dysfunction in Systemic Sclerosis.International journal of molecular sciences · 2023
    Review
  17. Article
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  19. The Role of Exposomes in the Pathophysiology of Autoimmune Diseases II: Pathogens.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022
    Review
  20. Review
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

6 authors.

Antonella FarinaDepartment of Experimental Medicine, Sapienza University, Rome, Italy.
Edoardo RosatoDepartment of Clinical Medicine, Sapienza University, Rome, Italy.
Michael YorkDivision of Rheumatology, Boston University School of Medicine, Boston, MA, United States.
Benjamin E GewurzDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Maria TrojanowskaDivision of Rheumatology, Boston University School of Medicine, Boston, MA, United States.
Giuseppina Alessandra FarinaDivision of Rheumatology, Boston University School of Medicine, Boston, MA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Microvascular injury is considered an initial event in the pathogenesis of scleroderma and endothelial cells are suspected of being the target of the autoimmune process seen in the disease. EBV has long been proposed as a trigger for autoimmune diseases, including scleroderma. Nevertheless, its contribution to the pathogenic process remains poorly understood. In this study, we report that EBV lytic antigens are detected in scleroderma dermal vessels, suggesting that endothelial cells might represent a target for EBV infection in scleroderma skin. We show that EBV DNA load is remarkably increased in peripheral blood, plasma and circulating monocytes from scleroderma patients compared to healthy EBV carriers, and that monocytes represent the prominent subsets of EBV-infected cells in scleroderma. Given that monocytes have the capacity to adhere to the endothelium, we then investigated whether monocyte-associated EBV could infect primary human endothelial cells. We demonstrated that endothelial cells are infectable by EBV, using human monocytes bound to recombinant EBV as a shuttle, even though cell-free virus failed to infect them. We show that EBV induces activation of TLR9 innate immune response and markers of vascular injury in infected endothelial cells and that up-regulation is associated with the expression of EBV lytic genes in infected cells. EBV innate immune modulation suggests a novel mechanism mediating inflammation, by which EBV triggers endothelial cell and vascular injury in scleroderma. In addition, our data point to up-regulation of EBV DNA loads as potential biomarker in developing vasculopathy in scleroderma. These findings provide the framework for the development of novel therapeutic interventions to shift the scleroderma treatment paradigm towards antiviral therapies.

Indexed as

Immunity, InnateAdultAgedBiopsyDNA, ViralEndothelial CellsEndothelium, VascularEpstein-Barr Virus InfectionsFemaleHerpesvirus 4, HumanHumansMaleMiddle AgedMonocytesScleroderma, SystemicSkinDNA, ViralTLR9 protein, humanToll-Like Receptor 9digital ulcersEBV DNA loadendothelial cellsEpstein-Barr Virusmonocytesscleroderma/SScTLR9 innate immune responsevascular injury

Identifiers

PMID33953718
PMCPMC8089375

What OpenQuestion holds

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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.