Evidence map›Paper›PMID 38969707›Full record

ArticleScientific reports2024

Evidence of membranolytic targeting and intracellular citrullination in neutrophils isolated from patients with rheumatoid arthritis.

Fatemeh Moadab, Xiaoxing Wang, Ethan Le, Tal Gazitt, Rayan Najjar, J Lee Nelson, Vijay Joshua, Vivianne Malmström, Keith Elkon, Caroline Grönwall and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

11 authors.

Fatemeh MoadabDivision of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108, USA.
Xiaoxing WangDivision of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108, USA.
Ethan LeDivision of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108, USA.
Tal GazittDivision of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108, USA.
Rayan NajjarDivision of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108, USA.
J Lee NelsonDivision of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108, USA.
Vijay JoshuaDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Vivianne MalmströmDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Keith ElkonDivision of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108, USA.
Caroline GrönwallDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Tomas MustelinDivision of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108, USA. tomas2@uw.edu.

Funding

RESEARCH TRAINING IN RHEUMATOLOGYT32AR007108 · NIAMS · UNIVERSITY OF WASHINGTON · PI Shaun Jackson, Tomas M Mustelin · 1986 to 2026
$6.6M
Role of the L1 retrotransposon in interferon-positive SLER01AR081654 · NIAMS · UNIVERSITY OF WASHINGTON · PI Tomas M Mustelin · 2023 to 2026
$2.1M
Role of protein citrullination in rheumatoid arthritisR01AR074939 · NIAMS · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2020 to 2024
$1.9M
Using Bioinformatics Methodologies to Explore the Role of Short Interspersed Elements in the Pathogenesis of Idiopathic Inflammatory MyopathiesK08AR082939 · NIAMS · UNIVERSITY OF WASHINGTON · PI Rayan Najjar · 2024 to 2026
$494k
The roots of SLE: Can we cure it with a reverse transcriptase inhibitor?R21AR075134 · NIAMS · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2019 to 2020
$427k
NIAMS NIH HHS R01 AR074939NIAMS NIH HHS T32 AR007108NIH HHS K08 AR082939NIH HHS R01 AR074939NIH HHS R01 AR081654NIH HHS R21 AR075134
6 · The paper itself

Abstract

Anti-citrullinated protein autoantibodies (ACPA) are diagnostic for rheumatoid arthritis (RA). The antigens recognized by these autoantibodies are produced by protein arginine deiminases (PADs), particularly PAD4. However, it remains unknown why and how PAD4 causes this aberrant citrullination in RA. Here, we report that poly-perforin pores are present on freshly isolated neutrophils from RA patients, but not on healthy donor neutrophils. Neutrophils with perforin pores also contained intracellular citrullinated proteins in the region adjacent to the pores. This response was replicated in vitro by treating neutrophils with purified perforin, which generated intense dots of anti-perforin immunofluorescence, calcium influx, and intracellular citrullination. Extensive neutrophil killing in Felty's syndrome, an aggressive form of RA, correlated with particularly high ACPA, and PAD4 autoantibodies. In contrast, other forms of death, including NETosis, apoptosis, and pyroptosis, produced minimal citrullination. We conclude that neutrophil targeting by perforin leading to intracellular citrullination takes place in patients with RA.

Indexed as

Anti-Citrullinated Protein AntibodiesArthritis, RheumatoidCitrullinationNeutrophilsPerforinProtein-Arginine Deiminase Type 4AdultAgedAutoantibodiesCitrullineExtracellular TrapsFelty SyndromeFemaleHumansMaleMiddle AgedAnti-Citrullinated Protein AntibodiesAutoantibodiesCitrullinePADI4 protein, humanPerforinProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4

Identifiers

PMID38969707
PMCPMC11226660

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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.