Evidence map›Paper›PMID 36828807›Full record

ArticleNature communications2023

Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis.

Ashley M Curran, Alexander A Girgis, Yura Jang, Jonathan D Crawford, Mekha A Thomas, Ryan Kawalerski, Jeff Coller, Clifton O Bingham, Chan Hyun Na, Erika Darrah

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

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
12.4field-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

39 citing papers in PubMed, 50 citations in OpenAlex.

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  5. mMolecular medicine reports · 2026
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  19. Impact of Periodontal Treatment on Early Rheumatoid Arthritis and the Role of Porphyromonas gingivalis Antibody Titers.Medical science monitor : international medical journal of experimental and clinical research · 2025
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Ashley M CurranRheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-7735-0437
Alexander A GirgisRheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-4706-5480
Yura JangNeurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jonathan D CrawfordRheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-7614-9424
Mekha A ThomasRheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-5169-6568
Ryan KawalerskiBiomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Jeff CollerMolecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-5662-8110
Clifton O BinghamRheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chan Hyun NaNeurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-3622-2938
Erika DarrahRheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. edarrah1@jhmi.edu.ORCID 0000-0003-1119-0279
Johns Hopkins University · USCenter for Drug Evaluation and Research · US

Funding

Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
Sample Processing and Immunoassay Research CoreP30AR070254 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CLIFTON O BINGHAM, Antony Rosen · 2016 to 2026
$8.9M
The role of cytotoxic T cells in rheumatoid arthritis pathogenesisR01AR079404 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI ANDRADE, FELIPE · 2021 to 2025
$2.9M
Fourier Transform Orbitrap Fusion Lumos Tribrid Mass Spectrometer with ETDS10OD021844 · OD · JOHNS HOPKINS UNIVERSITY · PI PANDEY, AKHILESH · 2016 to 2016
$1.1M
NIAMS NIH HHS P30 AR070254NIAMS NIH HHS R01 AR079404NIGMS NIH HHS T32 GM136577NIH HHS S10 OD021844
6 · The paper itself

Abstract

Cryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and hypothesized to drive the loss of immune tolerance to self-antigens in autoimmunity. Rheumatoid arthritis (RA) is an autoimmune disease characterized by immune responses to citrullinated self-antigens, in which arginine residues are converted to citrullines. Here, we investigate the hypothesis that citrullination exposes cryptic peptides by modifying protein structure and proteolytic cleavage. We show that citrullination alters processing and presentation of autoantigens, resulting in the generation of a unique citrullination-dependent repertoire composed primarily of native sequences. This repertoire stimulates T cells from RA patients with anti-citrullinated protein antibodies more robustly than controls. The generation of this unique repertoire is achieved through altered protease cleavage and protein destabilization, rather than direct presentation of citrulline-containing epitopes, suggesting a novel paradigm for the role of protein citrullination in the breach of immune tolerance in RA.

Indexed as

Arthritis, RheumatoidCitrullinationAntigen PresentationAutoantigensCitrullineEpitopesHumansPeptidesAutoantigensCitrullineEpitopesPeptides

Identifiers

PMID36828807
PMCPMC9958131
OpenAlexW4321791260

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.