Evidence map›Paper›PMID 40908179›Full record

ArticleEBioMedicine2025

Specific features of immune ageing are detected in the earliest stages in rheumatoid arthritis development.

Karim Raza, Archana Sharma-Oates, Leonid Padyukov, Annette H M van der Helm-van Mil, Arthur G Pratt, Simon W Jones, A Filer, Janet M Lord, Niharika A Duggal

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In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
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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

9 authors.

Karim RazaDepartment of Inflammation and Ageing, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham, UK; Department of Rheumatology, Sandwell and West Birmingham NHS Trust, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham and University of Birmingham, Birmingham, UK.
Archana Sharma-OatesSchool of Biosciences, University of Birmingham, Birmingham, UK.
Leonid PadyukovDivision of Rheumatology, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
Annette H M van der Helm-van MilLeiden University Medical Center, Leiden, Netherlands.
Arthur G PrattInstitute of Translational and Clinical Research, Newcastle University, Newcastle-upon-Tyne, UK.
Simon W JonesDepartment of Inflammation and Ageing, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham, UK; MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham and University of Birmingham, Birmingham, UK.
A FilerDepartment of Inflammation and Ageing, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham and University of Birmingham, Birmingham, UK.
Janet M LordDepartment of Inflammation and Ageing, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham, UK; MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham and University of Birmingham, Birmingham, UK.
Niharika A DuggalDepartment of Inflammation and Ageing, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham, UK; MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham and University of Birmingham, Birmingham, UK. Electronic address: aroran@bham.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRheumatoid arthritis is an age-related disease displaying features of an aged immune system. This study aims to determine premature presence of immune ageing in the early stages of RA development, including in patients with clinically suspected arthralgia and undifferentiated arthritis.

methodsWe recruited 224 participants: 69 healthy controls (mean age 57.12 years, 28% male); 32 with clinically suspected arthralgia (mean age 46.50 years, 11% male); 44 with undifferentiated arthritis (mean age 51.96 years, 21% male); 23 with newly presenting DMARD naive RA and 3 months or less symptom duration (mean age 56.5 years, 30% male) and 56 with DMARD naive RA and greater than 3 months symptom duration (mean age 56.41 years, 41% male). Features of immune ageing were assessed via flow cytometry and a subset of 8 immune cell type frequencies were used to generate an integrated score of immune ageing IMM-AGE and transcriptomic analysis for hallmarks of immune ageing was performed.

findingsReduced frequencies of naive CD4 T cells and recent thymic emigrants were seen in patients with arthralgia or undifferentiated arthritis. Other features of immune ageing, such as raised frequency of Th17, Tregs and senescent-like T cells, were only seen once RA was established. Overall, the IMM-AGE score and other hallmarks of ageing (inflammation, autophagic defects) were raised in patients during early stages of the disease. Lastly, we have provided evidence of immune ageing features as a predictor of RA development in arthralgia patients.

interpretationWe have shown that some features of immune ageing are present in the very early stages of RA and may therefore contribute to disease development. Future research should determine whether geroprotective drugs such as spermidine (autophagy booster), senolytics (clearance of senescent cells) and metformin (attenuates inflammation and boosts autophagy) reduce progression of the disease in patients at risk of RA.

fundingThis study was funded by a grant from FOREUM and the European League Against Rheumatism (EULAR).

Indexed as

AgingArthritis, RheumatoidImmunosenescenceAdultAgedBiomarkersCase-Control StudiesFemaleHumansMaleMiddle AgedBiomarkersAge-related diseaseImmune ageingImmunesenescenceRheumatoid arthritis

Identifiers

PMID40908179
PMCPMC12789766

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Registered trials

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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.