Evidence map›Paper›PMID 41833332›Full record

ArticleThe Journal of rheumatology2026

Neutrophil Extracellular Trap Formation-Derived Peptidylarginine Deiminases in the Citrullination of Oral Bacteria to Promote Inflammation in Rheumatoid Arthritis.

Suman Acharya, R Camille Brewer, Alejandro M Gomez, Shady Younis, Mahesh Pandit, Shaghayegh Jahanbani, Orr Sharpe, Zelda Z Love, Maureen C Howard, Dana E Orange and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Suman AcharyaS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.
R Camille BrewerS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.
Alejandro M GomezS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.ORCID 0000-0003-4415-2615
Shady YounisS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.
Mahesh PanditS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.
Shaghayegh JahanbaniS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.
Orr SharpeS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.
Zelda Z LoveS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.
Maureen C HowardS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California.ORCID 0009-0004-6263-8218
Dana E OrangeD.E. Orange, MD, MSc, Rockefeller University, and Hospital for Special Surgery, New York, New York, USA.
William H RobinsonS. Acharya, PhD, R.C. Brewer, PhD, A.M. Gomez, PhD, S. Younis, PhD, M. Pandit, PhD, S. Jahanbani, PhD, O. Sharpe, MS, Z.Z. Love, PhD, M.C. Howard, PhD, W.H. Robinson, MD, PhD, Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, and VA Palo Alto Health Care System, Palo Alto, California; w.robinson@stanford.edu.ORCID 0000-0003-4385-704X

Funding

Investigating Mucosal Breaks in the Initiation and Progression of Rheumatoid ArthritisR01AR078268 · NIAMS · STANFORD UNIVERSITY · PI ORANGE, DANA ELIZABETH, ROBINSON, WILLIAM H · 2021 to 2025
$3.1M
NIAMS NIH HHS R01 AR078268
6 · The paper itself

Abstract

objectivePeriodontal disease (PD) is an established risk factor for rheumatoid arthritis (RA). The objective of this study is to identify how oral bacterial infections occurring in damaged periodontal tissue in PD can lead to joint inflammation and destruction in RA.

methodsFour separate commensal oral bacteria species were cultured with human neutrophils to induce neutrophil extracellular trap formation (NETosis). The resultant NETs contained neutrophil-derived peptidylarginine deiminase 4 (PAD4), which, within the NET milieu, became activated and mediated citrullination of both bacterial and neutrophil self-proteins. Citrullination was evaluated by adding rabbit anticitrulline antibody followed by Alexa Fluor 647-conjugated antirabbit IgG secondary antibody.

resultsOur data demonstrate that citrullinated oral bacteria induce Toll-like receptor 9 (TLR9)-spleen tyrosine kinase (Syk)-mediated human B cell activation, differentiation, proliferation, and antibody secretion, including the development of plasmablasts secreting anticitrullinated protein antibodies (ACPAs). Some ACPAs bind citrullinated oral bacteria to form immune complexes (ICs) that can activate monocyte-derived macrophages in vitro to differentiate into CD11b

conclusionOur data support the hypothesis that in RA patients with PD, citrullinated oral bacteria breach damaged periodontal tissue to enter the circulation and induce both innate and adaptive proinflammatory responses that promote synovial tissue destruction.

Indexed as

Arthritis, RheumatoidCitrullinationExtracellular TrapsHydrolasesInflammationNeutrophilsPeriodontal DiseasesAnimalsAnti-Citrullinated Protein AntibodiesB-LymphocytesCells, CulturedCitrullineHumansProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4Anti-Citrullinated Protein AntibodiesCitrullineHydrolasesPADI4 protein, humanProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4ACPAscitrullinationNETosisperiodontal diseaserheumatoid arthritis

Identifiers

PMID41833332
PMCPMC12994871

What OpenQuestion holds

Textmetadata
LicenceTDM
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.