Evidence map›Paper›PMID 26759164›Full record

ArticleArthritis research & therapy2016

Overexpression of TLR2 and TLR9 on monocyte subsets of active rheumatoid arthritis patients contributes to enhance responsiveness to TLR agonists.

Patricia Lacerte, Alexandre Brunet, Benoit Egarnes, Benjamin Duchêne, Jacques P Brown, Jean Gosselin

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

39 citing papers in PubMed, 82 citations in OpenAlex.

  1. Article
  2. Review
  3. TLR9: A Double-Dealing Toll-Like Receptor.ImmunoTargets and therapy · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Innate immune memory in inflammatory arthritis.Nature reviews. Rheumatology · 2023
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
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  14. Review
  15. 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

6 authors at 1 institution in 1 country.

Patricia LacerteLaboratory of Innate Immunology, Centre de recherche du CHU de Québec, Université Laval, Québec, QC, Canada. patricia_lacerte@hotmail.com.
Alexandre BrunetLaboratory of Innate Immunology, Centre de recherche du CHU de Québec, Université Laval, Québec, QC, Canada. Alexandre.Brunet@crchudequebec.ulaval.ca.
Benoit EgarnesLaboratory of Innate Immunology, Centre de recherche du CHU de Québec, Université Laval, Québec, QC, Canada. benoit.egarnes.1@ulaval.ca.
Benjamin DuchêneLaboratory of Innate Immunology, Centre de recherche du CHU de Québec, Université Laval, Québec, QC, Canada. Benjamin.Duchene.1@ulaval.ca.
Jacques P BrownDivision of Rheumatology, Centre Hospitalier Universitaire de Québec, Université Laval (CHUL), Québec, QC, Canada. jacques.brown@crchudequebec.ulaval.ca.
Jean GosselinLaboratory of Innate Immunology, Centre de recherche du CHU de Québec, Université Laval, Québec, QC, Canada. jean.gosselin@crchudequebec.ulaval.ca.
Université Laval · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundSynovial infiltration of monocytes is commonly associated with inflammation in rheumatoid arthritis (RA). Toll-like receptors (TLRs) are innate sensors that recognize cell debris and microbial components in host, a process contributing to maintain chronic inflammation in RA. We assessed the expression levels of TLR2 and TLR9 in monocyte subsets of active RA patients and characterized their cytokine profiles in response to synthetic and viral TLR2 and TLR9 agonists, including Epstein-Barr virus (EBV) which is suspected to contribute to RA symptoms.

methodsPrevalence of monocyte subsets CD14(++) CD16(-), CD14(+) CD16(+) and CD14(low) CD16(++) was evaluated in blood and synovial fluids of active RA patients and levels of TLR2 and TLR9 in monocyte subsets were measured by flow cytometry. Enriched monocytes derived from RA patients and healthy donors were stimulated in vitro with synthetic TLR2 and TLR9 agonists and with EBV particles or viral DNA. Intracellular cytokine profiles were determined in respective monocyte subsets. Finally, the presence of EBV genome was evaluated by real-time PCR in blood and synovial monocytes of RA patients.

resultsNumbers of CD14(+) CD16(+) and CD14(low) CD16(++) were found to increase in blood of RA patients compared to healthy controls, while all three subsets were detected in synovial fluids. TLR2 is abundantly expressed on blood and synovial CD14(++) CD16(-) and CD14(+) CD16(+) monocytes from RA patients. Levels of TLR9 were increased on all three subsets of blood monocytes but markedly enhanced in monocytes isolated from synovial fluids. Compared to healthy controls, CD14(++) CD16(-) monocytes of RA patients displayed an enlarged capacity to produce proinflammatory cytokines after stimulation with synthetic TLR2 and TLR9 agonists while both CD14(++) CD16(-) and CD14(+) CD16(+) monocytes showed increased response to EBV stimulation. The presence of EBV genome was also detected in monocytes and neutrophils of a significant proportion of patients.

conclusionPatients with active RA show an increased expression of TLR2 and TLR9 on monocyte subsets and display higher production of inflammatory cytokines in response to TLR agonists. The presence of EBV genome in monocytes and neutrophils reinforces the suspected role of the virus in the exacerbation of RA symptoms.

Indexed as

AgedArthritis, RheumatoidFemaleFlow CytometryGene Expression RegulationHumansInflammation MediatorsLipopolysaccharidesMaleMiddle AgedMonocytesTeichoic AcidsToll-Like Receptor 2Toll-Like Receptor 9Treatment OutcomeInflammation MediatorsLipopolysaccharideslipoteichoic acidTeichoic AcidsTLR2 protein, humanTLR9 protein, humanToll-Like Receptor 2Toll-Like Receptor 9

Identifiers

PMID26759164
PMCPMC4718023
OpenAlexW2236445422

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.