ArticleScience translational medicine2025
Progression to rheumatoid arthritis in at-risk individuals is defined by systemic inflammation and by T and B cell dysregulation.
Abstract read
In one paragraph
Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.
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.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Autoantibodies as predictors of progression to rheumatoid arthritis: a systematic review and meta-analysis.RMD open · 2026Pooled it
- Abatacept versus hydroxychloroquine for prevention of rheumatoid arthritis in individuals with palindromic rheumatism: a randomized open-label trial.Nature medicine · 2026Trial
- Review
- Why a positive rheumatoid factor test does not always mean rheumatoid arthritis.The Journal of clinical investigation · 2026Article
- Rheumatoid factor production is genetically and molecularly distinct from rheumatoid arthritis.The Journal of clinical investigation · 2026Article
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- scVIP: personalized modeling of single-cell transcriptomes for developmental and disease phenotypes.bioRxiv : the preprint server for biology · 2026Article
- T-cell subset biomarkers across the rheumatoid arthritis disease continuum: from clinical utility to adoption in daily practice.Rheumatology (Oxford, England) · 2026Article
- NLRP3 inflammasome promotes PAD2/PAD4 release and protein citrullination in rheumatoid arthritis.Communications biology · 2026Article
- Longitudinal peripheral blood multi-omic profiling in seropositive individuals identifies immune endotypes and predictive models for future rheumatoid arthritis conversion.medRxiv : the preprint server for health sciences · 2026Article
- Advances in understanding preclinical rheumatoid arthritis and prospects for prevention.Nature reviews. Rheumatology · 2026Article
- Soluble IL-2 receptor and memory Treg profiles differentiate early rheumatoid arthritis from undifferentiated arthritis at initial presentation.Frontiers in immunology · 2026Article
- Article
- PULSAR: a Foundation Model for Multi-scale and Multi-cellular Biology.bioRxiv : the preprint server for biology · 2025Article
- Using mass cytometry to probe the STAT signaling landscape in circulating immune cells in Rheumatoid Arthritis uncovers signaling dysregulation and correlation with disease activity.Frontiers in medicine · 2025Article
Corrections and comments
- Update of
Authors and funding
77 authors.
Ziyuan HeAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-3556-8248
Marla C GlassAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-3763-0842
Pravina VenkatesanAllen Institute for Immunology, Seattle, WA 98109, USA.
Marie L FeserUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0009-0003-0598-853X
Leander LazaroUniversity of California, San Diego, San Diego, CA 92093, USA.ORCID 0009-0001-8075-9062
Lauren Y OkadaAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-5691-3373
Nhung T T TranAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-9660-8904
Yudong D HeAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-0818-605X
Samir Rachid ZaimAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0007-9256-2324
Christy E BennettAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0000-1477-7126
Padmapriyadarshini RavisankarAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-7061-9875
Elisabeth M DornischAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0009-6969-8690
Alexandra C FerranniniAllen Institute for Immunology, Seattle, WA 98109, USA.
Najeeb A ArishiUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.
Ashley G AsamoahUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.
Saman BarzidehUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.
Lynne A BeckerAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-1541-4655
Elizabeth A BemisUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0002-3556-3175
Jane H BucknerBRI Center for Interventional Immunology, Seattle, WA 98101, USA.ORCID 0000-0002-9005-1885
Christopher E ColloraUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0009-0000-0183-3475
Megan A L CrileyUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.
M Kristen DemoruelleUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0002-2563-5155
Chelsie L FleischerUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0001-5706-7618
Jessica GarberAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0007-8773-9754
Palak C GengeAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-0851-6445
Qiuyu GongAllen Institute for Immunology, Seattle, WA 98109, USA.
Lucas T GraybuckAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-8814-6818
Claire E GustafsonAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-1437-6709
Brian C HattelUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0009-0000-3015-2425
Veronica HernandezAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-2568-2565
Alexander T HeubeckAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-9312-4090
Erin K KaweloAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0004-0329-9914
Upaasana KrishnanAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0001-8589-7061
Emma L KuanAllen Institute for Immunology, Seattle, WA 98109, USA.
Kristine A KuhnUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0002-6900-4195
Christian M LaFranceAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0006-0763-2002
Kevin J LeeAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0001-9539-764X
Ruoxin LiAllen Institute for Immunology, Seattle, WA 98109, USA.
Cara LordAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-7827-2159
Regina R MetteyAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0003-7210-7595
Laura MossUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.
Blessing MusgroveAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0000-0640-723X
Katherine Hy NguyenUniversity of California, San Diego, San Diego, CA 92093, USA.
Andrea OchoaUniversity of California, San Diego, San Diego, CA 92093, USA.
Vaishnavi ParthasarathyAllen Institute for Immunology, Seattle, WA 98109, USA.
Mark-Phillip PebworthAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0001-8224-9480
Chong PedrickUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.
Tao PengAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-0550-9183
Cole G PhalenAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-0196-2805
Julian ReadingAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-8533-3992
Charles R RollAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-0726-2076
Jennifer A SeifertUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0001-5851-7246
Marguerite D SiedschlagUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.
Cate SpeakeBRI Center for Interventional Immunology, Seattle, WA 98101, USA.ORCID 0000-0003-1480-4272
Christopher C StriebichUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0003-2582-7752
Tyanna J StuckeyAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0009-0003-3262-8441
Elliott G SwansonAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-0351-6446
Hideto TakadaUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0009-0005-4541-2636
Tylor ThaiUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0009-0009-4159-4427
Zachary J ThomsonAllen Institute for Immunology, Seattle, WA 98109, USA.
Nguyen TrieuUniversity of California, San Diego, San Diego, CA 92093, USA.
Vlad TsaltskanUniversity of California, San Diego, San Diego, CA 92093, USA.ORCID 0000-0002-1359-0674
Wei WangUniversity of California, San Diego, San Diego, CA 92093, USA.ORCID 0000-0003-4377-5060
Morgan D A WeissAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0002-4189-1992
Amy WestermannUniversity of California, San Diego, San Diego, CA 92093, USA.ORCID 0000-0003-1209-4043
Fan ZhangUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0002-6102-2970
David L BoyleUniversity of California, San Diego, San Diego, CA 92093, USA.
Ananda W GoldrathAllen Institute for Immunology, Seattle, WA 98109, USA.
Thomas F BumolAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-4319-1006
Xiao-Jun LiAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-0832-9479
V Michael HolersUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0002-5634-7746
Peter J SkeneAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0001-8965-5326
Adam K SavageAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-1913-5485
Gary S FiresteinUniversity of California, San Diego, San Diego, CA 92093, USA.ORCID 0000-0003-3495-960X
Kevin D DeaneUniversity of Colorado Anschutz Medical Campus, Aurora CO 80045, USA.ORCID 0000-0003-2211-4861
Troy R TorgersonAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0003-3489-5036
Mark A GillespieAllen Institute for Immunology, Seattle, WA 98109, USA.ORCID 0000-0001-7820-8598
Funding
Core 2 - Mucosal Immunobiology Core (MIC)P30AR079369 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI Vernon Michael Holers · 2021 to 2026
$4.7MDeciphering Complement-Dependent Macrophage Phenotypes in Human Autoimmune ArthritisR01AR085156 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI FAN ZHANG · 2025 to 2026
$766kNIAMS NIH HHS P30 AR079369NIAMS NIH HHS R01 AR085156
Abstract
Rheumatoid arthritis (RA) is preceded by an at-risk stage of disease that can be marked by the presence of anticitrullinated protein antibodies (ACPAs) but the absence of clinically apparent synovitis (clinical RA). Preemptive intervention in at-risk individuals could prevent or delay future tissue damage; however, the immunobiology of this stage is unclear. Using integrative multiomics, we longitudinally profiled at-risk individuals, where one-third of participants developed clinical RA on study. We found evidence of systemic inflammation and signatures of activation in naïve T and B cells of at-risk individuals. During progression to clinical RA, proinflammatory skewing of atypical B cells and expansion of memory CD4 T cells with signatures of activation and B cell help were present without elevations in circulating ACPA titers. Epigenetic changes in naïve CD4 T cells suggested a predisposition to differentiate into effector cells capable of B cell help. These findings characterize pathogenesis of the ACPA
Indexed as
Arthritis, RheumatoidB-LymphocytesDisease ProgressionInflammationT-LymphocytesAdultCD4-Positive T-LymphocytesEpigenesis, GeneticFemaleHumansMaleMiddle AgedRisk Factors
Identifiers
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.