Evidence map›Paper›PMID 38630712›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

The monocyte cell surface is a unique site of autoantigen generation in rheumatoid arthritis.

Mekha A Thomas, Pooja Naik, Hong Wang, Jon T Giles, Alexander A Girgis, Seok-Young Kim, Tory P Johnson, Ashley M Curran, Jonathan D Crawford, Shaghayegh Jahanbani and 4 more

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

6 citing papers in PubMed, 3 citations in OpenAlex.

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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

14 authors at 4 institutions in 1 country.

Mekha A ThomasDivision of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.ORCID 0000-0002-5169-6568
Pooja NaikDivision of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.ORCID 0000-0002-2753-7129
Hong WangDivision of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.
Jon T GilesDivision of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Alexander A GirgisDivision of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.ORCID 0000-0002-4706-5480
Seok-Young KimDepartment of Neurology, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205.ORCID 0000-0001-6529-0115
Tory P JohnsonSection of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892.
Ashley M CurranDivision of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.ORCID 0000-0001-7735-0437
Jonathan D CrawfordDivision of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.
Shaghayegh JahanbaniDivision of Immunology and Rheumatology, Stanford University, Stanford, CA 94304.ORCID 0000-0001-7789-4856
Clifton O BinghamDivision of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.ORCID 0000-0002-4752-5029
William H RobinsonDivision of Immunology and Rheumatology, Stanford University, Stanford, CA 94304.ORCID 0000-0003-4385-704X
Chan Hyun NaDepartment of Neurology, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205.
Erika DarrahDivision of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.ORCID 0000-0003-1119-0279
Johns Hopkins University · USVA Palo Alto Health Care System · USColumbia University · USNational Institute of Neurological Disorders and Stroke · US

Funding

Sample Processing and Immunoassay Research CoreP30AR070254 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CLIFTON O BINGHAM, Antony Rosen · 2016 to 2026
$8.9M
Prevention Center U01: Early Targets for Antigen-Specific Tolerance Induction in Preclinical Rheumatoid ArthritisU01AI101981 · NIAID · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2012 to 2021
$6.2M
Ultra-Fast Epigenomic Maps for Monitoring AutoimmunityU19AI110491 · NIAID · STANFORD UNIVERSITY · PI UTZ, PAUL JOSEPH · 2014 to 2018
$3.6M
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
Fourier Transform Orbitrap Fusion Lumos Tribrid Mass Spectrometer with ETDS10OD021844 · OD · JOHNS HOPKINS UNIVERSITY · PI PANDEY, AKHILESH · 2016 to 2016
$1.1M
NIAID NIH HHS U01 AI101981NIAID NIH HHS U19 AI110491NIAMS NIH HHS P30 AR070254NIAMS NIH HHS R01 AR078268NIH HHS S10 OD021844
6 · The paper itself

Abstract

Although anti-citrullinated protein autoantibodies (ACPAs) are a hallmark serological feature of rheumatoid arthritis (RA), the mechanisms and cellular sources behind the generation of the RA citrullinome remain incompletely defined. Peptidylarginine deiminase IV (PAD4), one of the key enzymatic drivers of citrullination in the RA joint, is expressed by granulocytes and monocytes; however, the subcellular localization and contribution of monocyte-derived PAD4 to the generation of citrullinated autoantigens remain underexplored. In this study, we demonstrate that PAD4 displays a widespread cellular distribution in monocytes, including expression on the cell surface. Surface PAD4 was enzymatically active and capable of citrullinating extracellular fibrinogen and endogenous surface proteins in a calcium dose-dependent manner. Fibrinogen citrullinated by monocyte-surface PAD4 could be specifically recognized over native fibrinogen by a panel of eight human monoclonal ACPAs. Several unique PAD4 substrates were identified on the monocyte surface via mass spectrometry, with citrullination of the CD11b and CD18 components of the Mac-1 integrin complex being the most abundant. Citrullinated Mac-1 was found to be a target of ACPAs in 25% of RA patients, and Mac-1 ACPAs were significantly associated with HLA-DRB1 shared epitope alleles, higher C-reactive protein and IL-6 levels, and more erosive joint damage. Our findings implicate the monocyte cell surface as a unique and consequential site of extracellular and cell surface autoantigen generation in RA.

Indexed as

Aminosalicylic AcidsArthritis, RheumatoidMonocytesAutoantibodiesAutoantigensCitrullineFibrinogenHumansProtein-Arginine Deiminasesacetyl 4-aminosalicylic acidAminosalicylic AcidsAutoantibodiesAutoantigensCitrullineFibrinogenProtein-Arginine Deiminasesautoantibodiescitrullinationmonocytespeptidylarginine deiminaserheumatoid arthritis

Identifiers

PMID38630712
PMCPMC11047081
OpenAlexW4394874512

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.