Evidence map›Paper›PMID 34112702›Full record

ArticleRMD open2021

Tocilizumab decreases T cells but not macrophages in the synovium of patients with rheumatoid arthritis while it increases the levels of serum interleukin-6 and RANKL.

Katerina Chatzidionysiou, Alexandra Circiumaru, Bence Rethi, Vijay Joshua, Marianne Engstrom, Aase Hensvold, Erik Af Klint, Anca Catrina

Open access · goldAbstract read
In one paragraph

Article in RMD open, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

8 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Resolution of inflammation during rheumatoid arthritis.Frontiers in cell and developmental biology · 2025
    Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. 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

8 authors at 2 institutions in 1 country.

Katerina ChatzidionysiouRheumatology Unit, Department of Gastroentorogy, Dematology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden aikaterini.chatzidionysiou@ki.se.ORCID 0000-0002-2669-1247
Alexandra CirciumaruDepartment of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
Bence RethiDepartment of Medicine Solna, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0001-8220-5015
Vijay JoshuaDepartment of Medicine Solna, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0002-2606-8180
Marianne EngstromDepartment of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
Aase HensvoldDepartment of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
Erik Af KlintRheumatology Unit, Department of Gastroentorogy, Dematology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Anca CatrinaRheumatology Unit, Department of Gastroentorogy, Dematology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.ORCID 0000-0002-1292-1152
Karolinska Institutet · SEKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesOur knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.

methods15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment.

resultsDisease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders.

conclusionsTCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.

Indexed as

Arthritis, RheumatoidInterleukin-6RANK LigandAntibodies, Monoclonal, HumanizedHumansMacrophagesReceptor Activator of Nuclear Factor-kappa BSynovial MembraneT-LymphocytesAntibodies, Monoclonal, HumanizedIL6 protein, humanInterleukin-6RANK LigandReceptor Activator of Nuclear Factor-kappa BTNFSF11 protein, humantocilizumabarthritisrheumatoidsynovitistreatment

Identifiers

PMID34112702
PMCPMC8194335
OpenAlexW3166411535

What OpenQuestion holds

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LicenceCC BY
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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.