Evidence map›Paper›PMID 25649145›Full record

ArticleAnnals of the rheumatic diseases2016

IL-6-driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anticitrullinated peptide antibody-negative rheumatoid arthritis.

Amy E Anderson, Arthur G Pratt, Mamdouh A K Sedhom, John Paul Doran, Christine Routledge, Ben Hargreaves, Philip M Brown, Kim-Anh Lê Cao, John D Isaacs, Ranjeny Thomas

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.7field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 74 citations in OpenAlex.

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  20. Inflammaging: Age and Systemic, Cellular, and Nuclear Inflammatory Biology in Older Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2019
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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

10 authors at 4 institutions in 2 countries.

Amy E AndersonNational Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Arthur G PrattNational Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Mamdouh A K SedhomThe University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia.
John Paul DoranNational Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Christine RoutledgeNational Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Ben HargreavesNational Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Philip M BrownNational Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Kim-Anh Lê CaoThe University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia.
John D IsaacsNational Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
Ranjeny ThomasThe University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia.
Newcastle upon Tyne Hospitals NHS Foundation Trust · GBUniversity of Queensland · AUNational Institute for Health Research · GBNIHR Newcastle Biomedical Research Centre · GB

Funding

Medical Research Council G1001518
6 · The paper itself

Abstract

objectivesA previously identified signal transduction and activator of transcription-3 (STAT3) target-enriched gene signature in circulating CD4+ T cells of patients with early rheumatoid arthritis (RA) was prominent in autoantibody-negative individuals. Here, interleukin (IL)-6-mediated STAT signalling was investigated in circulating lymphocytes of an independent early arthritis patient cohort, seeking further insight into RA pathogenesis and biomarkers of potential clinical utility.

methodsConstitutive and IL-6-induced expression of phosphorylated STAT1 (pSTAT1) and pSTAT3 was determined in T and B cells using Phosflow cytometric analysis in patients with RA and controls. Contemporaneous levels of serum cytokines were measured by immunoassay. Induced gene expression was measured in cultured CD4+T cells by quantitative real-time PCR.

resultsAmong circulating lymphocytes of 187 patients with early arthritis, constitutive pSTAT3 correlated with serum IL-6 levels maximally in CD4+ T cells. Increased constitutive pSTAT3, but not pSTAT1, was observed in circulating CD4+ T cells of patients with early anticitrullinated peptide autoantibody (ACPA)-negative RA compared with disease controls, and these levels decreased alongside markers of disease activity with IL-6R-targeted treatment. Among patients presenting with seronegative undifferentiated arthritis (UA) the ratio of constitutive pSTAT3:pSTAT1 in CD4+ T cells contributed substantially to an algorithm for predicting progression to classifiable RA during a median of 20 months follow-up (area under receiver operator characteristic curve=0.84; p<0.001).

conclusionsOur findings support a particular role for IL-6-driven CD4+ T cell activation via STAT3 during the induction of RA, particularly as a feature of ACPA-negative disease. CD4+ T cell pSTAT measurements show promise as biomarkers of UA-RA progression and now require independent validation.

Indexed as

AdolescentAdultAgedAged, 80 and overArthritis, RheumatoidAutoantibodiesBiomarkersB-LymphocytesCD4-Positive T-LymphocytesCytokinesDisease ProgressionFemaleHumansInterleukin-6MaleMiddle AgedAutoantibodiesBiomarkerscyclic citrullinated peptideCytokinesIL6 protein, humanInterleukin-6Peptides, CyclicSTAT1 protein, humanSTAT1 Transcription FactorSTAT3 Transcription FactorCytokinesEarly Rheumatoid ArthritisT Cells

Identifiers

PMID25649145
PMCPMC4752669
OpenAlexW2116558079

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.