Evidence map›Paper›PMID 34009274›Full record

Trial reportRheumatology (Oxford, England)2022

Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis.

Jonathan Aldridge, Kerstin Andersson, Inger Gjertsson, Anna-Karin Hultgård Ekwall, Magnus Hallström, Ronald van Vollenhoven, Anna-Carin Lundell, Anna Rudin

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Rheumatology (Oxford, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 29 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Review
  5. T follicular helper cells in primary immune regulatory disorders.The Journal of allergy and clinical immunology · 2025
    Review
  6. Review
  7. Article
  8. Transitional and CD21BMC rheumatology · 2025
    Article
  9. Article
  10. Resolution of inflammation during rheumatoid arthritis.Frontiers in cell and developmental biology · 2025
    Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Effect of DMARDs on the immunogenicity of vaccines.Nature reviews. Rheumatology · 2023
    Review
  16. Role of ceRNA network in inflammatory cells of rheumatoid arthritis.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023
    Article
  17. Role of sPD-1 and sPD-Ls in the pathogenesis of connective tissue disease.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023
    Article
  18. Review
  19. Review
  20. 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.

Jonathan AldridgeDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.ORCID 0000-0003-4580-9148
Kerstin AnderssonDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
Inger GjertssonDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
Anna-Karin Hultgård EkwallDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
Magnus HallströmDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
Ronald van VollenhovenDepartment of Medicine, Rheumatology Unit, Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
Anna-Carin LundellDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
Anna RudinDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
University of Gothenburg · SEKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTreatment with CTLA-4Ig blocks T-cell activation and is clinically effective in RA. However, it is unknown if specific CD4+ T-cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4+ T cells in patients with untreated early RA (eRA).

methodsThis study included 60 patients with untreated eRA from a larger randomized trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n = 17), anti-IL6 receptor (tocilizumab, n = 21) or anti-TNF (certolizumab-pegol, n = 22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI ≤ 2.8) at week 24. Proportions of 12 CD4+ T-cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24 weeks of treatment.

resultsIn patients treated with CTLA-4Ig, the proportions of PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline predicted CDAI remission at week 24. CD4+ T-cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24 weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1+T follicular helper (TFh) cells.

conclusionThese findings indicate that circulating proportions PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.

Indexed as

AbataceptAdultAgedAntibodies, Monoclonal, HumanizedAntirheumatic AgentsArthritis, RheumatoidBiomarkersCD4-Positive T-LymphocytesCertolizumab PegolCTLA-4 AntigenDrug Therapy, CombinationHumansMaleMethotrexateMiddle AgedProgrammed Cell Death 1 ReceptorAbataceptAntibodies, Monoclonal, HumanizedAntirheumatic AgentsBiomarkersCertolizumab PegolCTLA-4 AntigenMethotrexateProgrammed Cell Death 1 Receptortocilizumabanti-IL6Ranti-TNFCD4+CTLA-4IgremissionRheumatoid arthritisT cells

Identifiers

PMID34009274
PMCPMC8889294
OpenAlexW3161570650

What OpenQuestion holds

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LicenceCC BY-NC
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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.