Evidence map›Paper›PMID 28188029›Full record

ArticleJournal of autoimmunity2017

Peptidylarginine deiminase 2 is required for tumor necrosis factor alpha-induced citrullination and arthritis, but not neutrophil extracellular trap formation.

Mandar Bawadekar, Daeun Shim, Chad J Johnson, Thomas F Warner, Ryan Rebernick, Dres Damgaard, Claus H Nielsen, Ger J M Pruijn, Jeniel E Nett, Miriam A Shelef

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

Article in Journal of autoimmunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

55 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
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  3. Review
  4. Review
  5. Article
  6. Article
  7. Effects of neutrophil fate on inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Death of tonsillar B cells by NETosis.Cell death discovery · 2023
    Article
  13. Article
  14. Regulating Neutrophil PAD4/NOX-Dependent Cerebrovasular Thromboinflammation.International journal of biological sciences · 2023
    Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
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 3 institutions in 3 countries.

Mandar BawadekarDepartment of Medicine, University of Wisconsin, Madison, WI, USA.
Daeun ShimDepartment of Medicine, University of Wisconsin, Madison, WI, USA.
Chad J JohnsonDepartment of Medicine, University of Wisconsin, Madison, WI, USA.
Thomas F WarnerDepartment of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA.
Ryan RebernickDepartment of Medicine, University of Wisconsin, Madison, WI, USA.
Dres DamgaardInstitute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Claus H NielsenInstitute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Ger J M PruijnInstitute for Molecules and Materials and Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
Jeniel E NettDepartment of Medicine, University of Wisconsin, Madison, WI, USA; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
Miriam A ShelefDepartment of Medicine, University of Wisconsin, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. Electronic address: mshelef@medicine.wisc.edu.
University of Wisconsin–Madison · USCopenhagen University Hospital · DKRadboud University Nijmegen · NL

Funding

Mechanisms of Candida Biofilm Immune EvasionK08AI108727 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI NETT, JENIEL E · 2014 to 2018
$960k
PAD2 and PAD4 in Citrullination, Autoantibodies, and Rheumatoid ArthritisK08AR065500 · NIAMS · UNIVERSITY OF WISCONSIN-MADISON · PI SHELEF, MIRIAM ANNE · 2014 to 2018
$690k
NIAID NIH HHS K08 AI108727NIAMS NIH HHS K08 AR065500
6 · The paper itself

Abstract

Citrullination, the post-translational conversion of arginines to citrullines, may contribute to rheumatoid arthritis development given the generation of anti-citrullinated protein antibodies (ACPAs). However, it is not known which peptidylarginine deiminase (PAD) catalyzes the citrullination seen in inflammation. PAD4 exacerbates inflammatory arthritis and is critical for neutrophil extracellular traps (NETs). NETs display citrullinated antigens targeted by ACPAs and thus may be a source of citrullinated protein. However, PAD4 is not required for citrullination in inflamed lungs. PAD2 is important for citrullination in healthy tissues and is present in NETs, but its role in citrullination in the inflamed joint, NETosis and inflammatory arthritis is unknown. Here we use mice with TNFα-induced inflammatory arthritis, a model of rheumatoid arthritis, to identify the roles of PAD2 and PAD4 in citrullination, NETosis, and arthritis. In mice with TNFα-induced arthritis, citrullination in the inflamed ankle was increased as determined by western blot. This increase was unchanged in the ankles of mice that lack PAD4. In contrast, citrullination was nearly absent in the ankles of PAD2-deficient mice. Interestingly, PAD2 was not required for NET formation as assessed by immunofluorescence or for killing of Candida albicans as determined by viability assay. Finally, plasma cell numbers as assessed by flow cytometry, IgG levels quantified by ELISA, and inflammatory arthritis as determined by clinical and pathological scoring were all reduced in the absence of PAD2. Thus, PAD2 contributes to TNFα-induced citrullination and arthritis, but is not required for NETosis. In contrast, PAD4, which is critical for NETosis, is dispensable for generalized citrullination supporting the possibility that NETs may not be a major source of citrullinated protein in arthritis.

Indexed as

AnimalsAnti-Citrullinated Protein AntibodiesArthritis, ExperimentalArthritis, RheumatoidCitrullinationExtracellular TrapsHumansHydrolasesImmunoglobulin GInflammationJointsMiceMice, KnockoutMice, TransgenicPlasma CellsProtein-Arginine DeiminasesAnti-Citrullinated Protein AntibodiesHydrolasesImmunoglobulin Gpeptidylarginine deiminase 4, mouseProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4Tumor Necrosis Factor-alphaCitrullinationMurine modelNeutrophil extracellular trapPeptidylarginine deiminaseRheumatoid arthritisTNFα

Identifiers

PMID28188029
PMCPMC5422119
OpenAlexW2587650072

What OpenQuestion holds

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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.