Evidence map›Paper›PMID 37993439›Full record

ArticleNature communications2023

Multifaceted immune dysregulation characterizes individuals at-risk for rheumatoid arthritis.

Eddie A James, V Michael Holers, Radhika Iyer, E Barton Prideaux, Navin L Rao, Cliff Rims, Virginia S Muir, Sylvia E Posso, Michelle S Bloom, Amin Zia and 20 more

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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

17 citing papers in PubMed, 24 citations in OpenAlex.

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  4. TScience immunology · 2025
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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

30 authors at 7 institutions in 2 countries.

Eddie A James *Benaroya Research Institute, Seattle, WA, 98101, USA.ORCID 0000-0002-7217-5729
V Michael Holers *Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. michael.holers@cuanschutz.edu.
Radhika Iyer *Division of Immunology and Rheumatology, Stanford University, Stanford, CA, 94304, USA.ORCID 0000-0003-1287-3995
E Barton Prideaux *Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-8811-869X
Navin L RaoJanssen Research and Development, Spring House, PA, 19477, USA.
Cliff RimsBenaroya Research Institute, Seattle, WA, 98101, USA.
Virginia S MuirBenaroya Research Institute, Seattle, WA, 98101, USA.
Sylvia E PossoBenaroya Research Institute, Seattle, WA, 98101, USA.
Michelle S BloomDivision of Immunology and Rheumatology, Stanford University, Stanford, CA, 94304, USA.
Amin ZiaDivision of Immunology and Rheumatology, Stanford University, Stanford, CA, 94304, USA.ORCID 0000-0002-1239-0857
Serra E ElliottDivision of Immunology and Rheumatology, Stanford University, Stanford, CA, 94304, USA.
Julia Z AdamskaDivision of Immunology and Rheumatology, Stanford University, Stanford, CA, 94304, USA.ORCID 0000-0001-8657-4141
Rizi AiDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.
R Camille BrewerDivision of Immunology and Rheumatology, Stanford University, Stanford, CA, 94304, USA.ORCID 0000-0002-0342-1826
Jennifer A SeifertDivision of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
LauraKay MossDivision of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Saman BarzidehDivision of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
M Kristen DemoruelleDivision of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Christopher C StriebichDivision of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.ORCID 0000-0003-2582-7752
Yuko OkamotoDivision of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.ORCID 0000-0002-8088-1746
Enkhtsogt SainbayarDivision of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Alexandra A CrookDivision of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Ryan A PetersonDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.ORCID 0000-0002-4650-5798
Lauren A VanderlindenDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Wei WangDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0003-4377-5060
David L BoyleDivision of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, 92093, USA.
William H Robinson *Division of Immunology and Rheumatology, Stanford University, Stanford, CA, 94304, USA.
Jane H Buckner *Benaroya Research Institute, Seattle, WA, 98101, USA.ORCID 0000-0002-9005-1885
Gary S Firestein *Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0003-3495-960X
Kevin D Deane *Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.ORCID 0000-0003-2211-4861
University of Colorado Anschutz Medical Campus · USVA Palo Alto Health Care System · USBenaroya Research InstituteUniversity of California San Diego · USColorado School of Public Health · USJanssen (United States) · USTokyo Women's Medical University · JP

Funding

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
Identification of key regulators in rheumatoid arthritisR01AR065466 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, WANG, WEI · 2014 to 2024
$4.6M
Rheumatic Diseases Research Training GrantT32AR064194 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GARY S FIRESTEIN, Monica Guma · 2013 to 2026
$3.8M
NIAID NIH HHS U01 AI101981NIAMS NIH HHS R01 AR065466NIAMS NIH HHS T32 AR064194
6 · The paper itself

Abstract

Molecular markers of autoimmunity, such as antibodies to citrullinated protein antigens (ACPA), are detectable prior to inflammatory arthritis (IA) in rheumatoid arthritis (RA) and may define a state that is 'at-risk' for future RA. Here we present a cross-sectional comparative analysis among three groups that include ACPA positive individuals without IA (At-Risk), ACPA negative individuals and individuals with early, ACPA positive clinical RA (Early RA). Differential methylation analysis among the groups identifies non-specific dysregulation in peripheral B, memory and naïve T cells in At-Risk participants, with more specific immunological pathway abnormalities in Early RA. Tetramer studies show increased abundance of T cells recognizing citrullinated (cit) epitopes in At-Risk participants, including expansion of T cells reactive to citrullinated cartilage intermediate layer protein I (cit-CILP); these T cells have Th1, Th17, and T stem cell memory-like phenotypes. Antibody-antigen array analyses show that antibodies targeting cit-clusterin, cit-fibrinogen and cit-histone H4 are elevated in At-Risk and Early RA participants, with the highest levels of antibodies detected in those with Early RA. These findings indicate that an ACPA positive at-risk state is associated with multifaceted immune dysregulation that may represent a potential opportunity for targeted intervention.

Indexed as

Arthritis, RheumatoidAutoantibodiesCross-Sectional StudiesEpitopesHumansAutoantibodiesEpitopes

Identifiers

PMID37993439
PMCPMC10665556
OpenAlexW4388912002

What OpenQuestion holds

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Registered trials

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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.