ArticleThe Journal of clinical investigation2025
Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.
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Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Why a positive rheumatoid factor test does not always mean rheumatoid arthritis.The Journal of clinical investigation · 2026Article
- Specificity, frequency, and phenotype of citrullinated-specific T cells vary with disease activity in rheumatoid arthritis.JCI insight · 2026Article
- Immune responses in aging adults.The Journal of clinical investigation · 2026Review
- KLRB1 gene in tumor immune regulation and disease prognosis: a multidimensional role review.Discover oncology · 2026Review
- Innate lymphoid cells in rheumatoid arthritis as mediators of pathology and resolution.Nature reviews. Rheumatology · 2026Review
- Review
- scLASER: a robust framework for simulating and detecting time-dependent single-cell dynamics in longitudinal studies.bioRxiv : the preprint server for biology · 2026Article
- Preclinical Rheumatoid Arthritis: Pathogenesis, Risk Stratification, and Therapeutic Interception.Journal of clinical medicine · 2026Review
- 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
- HLA class I-naturally presented synovial tissue peptides are recognized by CD8+ T lymphocytes from rheumatoid arthritis patients.Frontiers in immunology · 2026Article
- Analysis of Cardiovascular Risk Factors in Patients with Psoriasis: A Cross-Sectional Study.Mediterranean journal of rheumatology · 2025Article
- Differential Neutrophil and Eosinophil Infiltrations in the Sub-Lining Compartment of Rheumatoid Versus Osteoarthritic Synovium.Mediterranean journal of rheumatology · 2025Article
- TScience immunology · 2025Article
- Immune-cell profiling to guide stratification and treatment of patients with rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- Mesenchymal stromal cells induce neutrophil aggregation and extracellular vesicle storms for systemic lupus erythematosus.Signal transduction and targeted therapy · 2025Article
- Progression to rheumatoid arthritis in at-risk individuals is defined by systemic inflammation and by T and B cell dysregulation.Science translational medicine · 2025Article
- Pathogenic Role of Cytokines in Rheumatoid Arthritis.Journal of clinical medicine · 2025Review
- Ectopic Nociceptor Sprouting as a Key Peripheral Driver of Pain in Rheumatoid Arthritis.Current rheumatology reports · 2025Review
- Review
Corrections and comments
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Authors and funding
43 authors.
Jun InamoDivision of Rheumatology and.
Joshua KeeganDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Alec GriffithDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Tusharkanti GhoshDepartment of Biostatistics & Informatics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Alice HorisbergerDepartment of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Kaitlyn HowardDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
John F PulfordDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ekaterina MurzinDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Brandon HancockDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Salina T DominguezDepartment of Medicine, Division of Rheumatology and.
Miranda G GurraDepartment of Preventive Medicine, Division of Biostatistics and Informatics, Northwestern University, Chicago, Illinois, USA.
Siddarth GurajalaBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Anna Helena JonssonDivision of Rheumatology and.
Jennifer A SeifertDivision of Rheumatology and.
Marie L FeserDivision of Rheumatology and.
Jill M NorrisDepartment of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.
Ye CaoDepartment of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
William ApruzzeseThe list of the Accelerating Medicines Partnership: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Program members is provided in Supplemental Acknowledgments.
S Louis BridgesDepartment of Medicine, Hospital for Special Surgery, New York, New York, USA.
Vivian P BykerkDepartment of Medicine, Hospital for Special Surgery, New York, New York, USA.
Susan GoodmanDepartment of Medicine, Hospital for Special Surgery, New York, New York, USA.
Laura T DonlinDepartment of Medicine, Hospital for Special Surgery, New York, New York, USA.
Gary S FiresteinDivision of Rheumatology, Allergy, and Immunology, UCSD, La Jolla, California, USA.
Joan M BathonDepartment of Medicine, Division of Rheumatology, Columbia University, New York, New York, USA.
Laura B HughesDepartment of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham Medicine, Birmingham, Alabama, USA.
Andrew FilerRheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
Costantino PitzalisCentre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London and Barts NIHR BRC & NHS Trust, London, United Kingdom.
Jennifer H AnolikDivision of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA.
Larry MorelandDivision of Rheumatology and.
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Joel M GuthridgeArthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Judith A JamesArthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Carla M CudaDepartment of Medicine, Division of Rheumatology and.
Harris PerlmanDepartment of Medicine, Division of Rheumatology and.
Michael B BrennerDepartment of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Soumya RaychaudhuriDepartment of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Jeffrey A SparksDepartment of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Accelerating Medicines Partnership RA/SLE Network
V Michael HolersDivision of Rheumatology and.
Kevin D DeaneDivision of Rheumatology and.
James LedererDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Deepak A RaoDepartment of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Fan ZhangDivision of Rheumatology and.
Funding
The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0MColorado Clinical and Translational Sciences Institute (CCTSI)UM1TR004399 · NCATS · UNIVERSITY OF COLORADO DENVER · PI JANINE A HIGGINS, RONALD J. SOKOL · 2023 to 2026
$30.7MAccelerating Medicines Partnership-Autoimmune and Immunologic Disease Tissue Research Core Admin Supplement: Preclinical Studies in Sjogren'sUC2AR081032 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI Joel Marvin Guthridge, JUDITH A JAMES · 2022 to 2026
$30.7MVERITY: Value and Evidence in Rheumatology using bioInformaTics, and advanced analYticsP30AR072577 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Daniel Hal Solomon · 2017 to 2026
$9.8MJoint Biology Consortium Resource-based CenterP30AR070253 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Peter A Nigrovic, Jeffrey Andrew Sparks · 2016 to 2026
$9.4MPEARL: Pathway Exploration and Analysis in Renal LupusUH2AR067688 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI DIAMOND, BETTY, WOFSY, DAVID · 2014 to 2020
$9.0MOklahoma Rheumatic Disease Research Cores Center (Overall Application)P30AR073750 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES · 2018 to 2026
$8.5MTissue Acquisition Research GroupUM2AR067678 · NIAMS · STANFORD UNIVERSITY · PI HOLERS, VERNON MICHAEL, UTZ, PAUL JOSEPH · 2014 to 2020
$8.2MMulti-Ethnic Translational Research Optimization (METRO) Lupus ConsortiumUH2AR067689 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BUYON, JILL P, PUTTERMAN, CHAIM · 2014 to 2020
$6.3MEvolving Adaptive and Effector Mechanisms from Pre-RA Through Established DiseaseUH2AR067681 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2014 to 2020
$5.5MMolecular and Cellular Dissection of Early Rheumatoid ArthritisUH2AR067694 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI BRENNER, MICHAEL B., GREGERSEN, PETER K. · 2014 to 2020
$5.4MCore 2 - Mucosal Immunobiology Core (MIC)P30AR079369 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI Vernon Michael Holers · 2021 to 2026
$4.7MNCATS NIH HHS UL1 TR002541NCATS NIH HHS UM1 TR004399NIAMS NIH HHS P30 AR070253NIAMS NIH HHS P30 AR072577NIAMS NIH HHS P30 AR073750NIAMS NIH HHS P30 AR079369NIAMS NIH HHS R01 AR077607NIAMS NIH HHS R01 AR080659NIAMS NIH HHS UC2 AR081032NIAMS NIH HHS UH2 AR067676NIAMS NIH HHS UH2 AR067677NIAMS NIH HHS UH2 AR067679NIAMS NIH HHS UH2 AR067681NIAMS NIH HHS UH2 AR067685NIAMS NIH HHS UH2 AR067688NIAMS NIH HHS UH2 AR067689NIAMS NIH HHS UH2 AR067690NIAMS NIH HHS UH2 AR067691NIAMS NIH HHS UH2 AR067694NIAMS NIH HHS UM2 AR067678
Abstract
Rheumatoid arthritis (RA) is a systemic autoimmune disease currently with no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in at-risk populations prior to clinical onset is crucial to establishing effective prevention strategies. Here, we applied multimodal single-cell technologies (mass cytometry and CITE-Seq) to characterize the immunophenotypes in blood from at-risk individuals (ARIs) identified through the presence of serum antibodies against citrullinated protein antigens (ACPAs) and/or first-degree relative (FDR) status, as compared with patients with established RA and people in a healthy control group. We identified significant cell expansions in ARIs compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5lo naive B cell population was expanded in ACPA-positive FDRs. Further, we uncovered the molecular phenotype of the CCR2+CD4+ T cells, expressing high levels of Th17- and Th22-related signature transcripts including CCR6, IL23R, KLRB1, CD96, and IL22. Our integrated study provides a promising approach to identify targets to improve prevention strategy development for RA.
Indexed as
Arthritis, RheumatoidB-LymphocytesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesImmunophenotypingLymphocyte ActivationTh17 CellsAdultAgedAnti-Citrullinated Protein AntibodiesCase-Control StudiesFemaleHumansMaleMiddle AgedAnti-Citrullinated Protein AntibodiesArthritisAutoimmunityBioinformaticsImmunologyRheumatology
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