Evidence map›Paper›PMID 36411473›Full record

ArticleArthritis research & therapy2022

The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis.

J Parantainen, G Barreto, R Koivuniemi, H Kautiainen, D Nordström, E Moilanen, M Hämäläinen, M Leirisalo-Repo, K Nurmi, K K Eklund

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  5. Journal of oral microbiology · 2026
    Review
  6. Total saponins ofJournal of ginseng research · 2025
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  10. Review
  11. Review
  12. Review
  13. Article
  14. Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritisFrontiers in cellular and infection microbiology · 2023
    Review
  15. Article
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 at 6 institutions in 1 country.

J ParantainenTranslational Immunology Research Program, Faculty of Medicine, University of Helsinki, PL 4 (Yliopistonkatu 3), 00014, Helsinki, Finland. jukka.parantainen@hus.fi.
G BarretoTranslational Immunology Research Program, Faculty of Medicine, University of Helsinki, PL 4 (Yliopistonkatu 3), 00014, Helsinki, Finland.
R KoivuniemiDepartment of Rheumatology, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
H KautiainenFolkhälsan Research Center, Helsinki, Finland; Unit of Primary Health Care, Kuopio University Hospital, Kuopio, Finland.
D NordströmDepartment of Internal medicine and rehabilitation, Helsinki University and Helsinki University Hospital, Helsinki, Finland.
E MoilanenThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
M HämäläinenThe Immunopharmacology Research Group, Faculty of Medicine and Health Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
M Leirisalo-RepoDepartment of Rheumatology, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
K Nurmi *Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, PL 4 (Yliopistonkatu 3), 00014, Helsinki, Finland.
K K Eklund *Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, PL 4 (Yliopistonkatu 3), 00014, Helsinki, Finland.
University of Helsinki · FIHelsinki University Hospital · FIInvalidisäätiö · FIKuopio University Hospital · FITampere University · FITampere University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of serum lipopolysaccharides (LPS) with disease activity and likelihood of achieving remission in RA patients.

methodsWe measured Toll-like receptor (TLR) 4-stimulating activity of sera of 58 RA patients with a reporter cell line engineered to produce secreted alkaline phosphatase in response to TLR4 stimulation. Levels of LPS-binding protein, CD14, and CD163 were determined by ELISA assays.

resultsThe patient serum-induced TLR4 activation (biological activity of LPS) was significantly associated with inflammatory parameters and body mass index at baseline and at 12 months and with disease activity (DAS28-CRP, p<0.001) at 12 months. Importantly, baseline LPS bioactivity correlated with disease activity (p=0.031) and, in 28 early RA patients, the likelihood of achieving remission at 12 months (p=0.009). The level of LPS bioactivity was similar at baseline and 12-month visits, suggesting that LPS bioactivity is an independent patient-related factor. Neutralization of LPS in serum by polymyxin B abrogated the TLR4 signaling, suggesting that LPS was the major contributor to TLR4 activation.

conclusionWe describe a novel approach to study the biological activity of serum LPS and their impact in diseases. The results suggest that LPS contribute to the inflammatory burden and disease activity on patients with RA and that serum-induced TLR4 activation assays can serve as an independent prognostic factor. A graphical summary of the conclusions of the study.

Indexed as

Arthritis, RheumatoidMicrobiotaHumansLipopolysaccharidesProbabilityRemission, SpontaneousToll-Like Receptor 4LipopolysaccharidesToll-Like Receptor 4DysbiosisLipopolysaccharidesRheumatoid arthritis

Identifiers

PMID36411473
PMCPMC9677706
OpenAlexW4309448491

What OpenQuestion holds

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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.