Evidence map›Paper›PMID 28128853›Full record

ArticleClinical and experimental immunology2017

Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis.

V C Willis, N K Banda, K N Cordova, P E Chandra, W H Robinson, D C Cooper, D Lugo, G Mehta, S Taylor, P P Tak and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical and experimental immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
10.2field-weighted citation impact, top 1% 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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Citrullination in tumor immunity and therapy.The Journal of clinical investigation · 2025
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024
    Review
  15. Article
  16. Review
  17. Article
  18. Citrullination and the protein code: crosstalk between post-translational modifications in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  19. An unbiased proteomic analysis of PAD4 in human monocytes: novel substrates, binding partners and subcellular localizations.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Article
  20. Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review

6 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 2 countries.

V C WillisDivision of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
N K BandaDivision of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
K N CordovaDivision of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
P E ChandraDivision of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA and the VA Palo Alto Health Care System, Palo Alto, CA, USA.
W H RobinsonDivision of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA and the VA Palo Alto Health Care System, Palo Alto, CA, USA.
D C CooperTarget Sciences Statistics, GlaxoSmithKline, Collegeville, PA, USA.
D LugoImmuno-Inflammation Therapy Area, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK.
G MehtaDivision of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
S TaylorImmuno-Inflammation Therapy Area, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK.
P P TakImmuno-Inflammation Therapy Area, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK.
R K PrinjhaImmuno-Inflammation Therapy Area, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK.
H D LewisImmuno-Inflammation Therapy Area, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK.
V M HolersDivision of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
GlaxoSmithKline (United Kingdom) · GBUniversity of Colorado Denver · USStanford University · USGlaxoSmithKline (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Citrullination of joint proteins by the protein arginine deiminase (PAD) family of enzymes is recognized increasingly as a key process in the pathogenesis of rheumatoid arthritis. This present study was undertaken to explore the efficacy of a novel PAD4-selective inhibitor, GSK199, in the murine collagen-induced arthritis model of rheumatoid arthritis. Mice were dosed daily from the time of collagen immunization with GSK199. Efficacy was assessed against a wide range of end-points, including clinical disease scores, joint histology and immunohistochemistry, serum and joint citrulline levels and quantification of synovial autoantibodies using a proteomic array containing joint peptides. Administration of GSK199 at 30 mg/kg led to significant effects on arthritis, assessed both by global clinical disease activity and by histological analyses of synovial inflammation, pannus formation and damage to cartilage and bone. In addition, significant decreases in complement C3 deposition in both synovium and cartilage were observed robustly with GSK199 at 10 mg/kg. Neither the total levels of citrulline measurable in joint and serum, nor levels of circulating collagen antibodies, were affected significantly by treatment with GSK199 at any dose level. In contrast, a subset of serum antibodies reactive against citrullinated and non-citrullinated joint peptides were reduced with GSK199 treatment. These data extend our previous demonstration of efficacy with the pan-PAD inhibitor Cl-amidine and demonstrate robustly that PAD4 inhibition alone is sufficient to block murine arthritis clinical and histopathological end-points.

Indexed as

AnimalsArthritis, ExperimentalArthritis, RheumatoidAutoantibodiesBenzimidazolesBone and BonesCartilageCitrullineCollagenComplement C3HydrolasesMiceProtein-Arginine Deiminase Type 4ProteomicsSynovial MembraneAutoantibodiesBenzimidazolesCitrullineCollagenComplement C3GSK199Hydrolasespeptidylarginine deiminase 4, mouseProtein-Arginine Deiminase Type 4ACPAcitrullinationcomplementPAD4rheumatoid arthritis

Identifiers

PMID28128853
PMCPMC5383440
OpenAlexW2582017063

What OpenQuestion holds

Textmetadata
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.