Evidence map›Paper›PMID 28863153›Full record

ArticlePloS one2017

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways.

Alice M Walsh, Mihir D Wechalekar, Yanxia Guo, Xuefeng Yin, Helen Weedon, Susanna M Proudman, Malcolm D Smith, Sunil Nagpal

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. 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
3.1field-weighted citation impact, top 8% 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, 53 citations in OpenAlex.

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  16. Bub1 suppresses inflammatory arthritis-associated bone loss in mice through inhibition of TNFα-mediated osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
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  17. BuDDI:bioRxiv : the preprint server for biology · 2024
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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

8 authors at 3 institutions in 2 countries.

Alice M WalshImmunology, Janssen Research and Development, LLC., Spring House, Pennsylvania, United States of America.ORCID http://orcid.org/0000-0001-5905-5768
Mihir D WechalekarRepatriation General Hospital, Daw Park, South Australia, Australia.
Yanxia GuoImmunology, Janssen Research and Development, LLC., Spring House, Pennsylvania, United States of America.
Xuefeng YinImmunology, Janssen Research and Development, LLC., Spring House, Pennsylvania, United States of America.
Helen WeedonFlinders University, Adelaide, South Australia, Australia.
Susanna M ProudmanRheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Malcolm D SmithFlinders University, Adelaide, South Australia, Australia.
Sunil NagpalImmunology, Janssen Research and Development, LLC., Spring House, Pennsylvania, United States of America.
Janssen (United States) · USFlinders University · AURoyal Adelaide Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThis study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown.

methodsPaired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing.

resultsLarge differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function.

conclusionsWe have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission.

Indexed as

AdultAgedAntirheumatic AgentsArthritis, RheumatoidArthroscopyBiopsyCase-Control StudiesCell DifferentiationDown-RegulationDrug Therapy, CombinationFemaleHumansHydroxychloroquineLymphocyte ActivationMaleMethotrexateAntirheumatic AgentsHydroxychloroquineMethotrexateSulfasalazine

Identifiers

PMID28863153
PMCPMC5580991
OpenAlexW2752679580

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.