ArticleThe New England journal of medicine2020
RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02051114 (Discovering the Antecedents of Rheumatoid Arthritis Flare), which is not on this map. Cited by 111 papers.
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111citing papers in PubMed
20.5field-weighted citation impact, top 1% of its field
What it found
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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.
Discovering the Antecedents of Rheumatoid Arthritis Flare
Who cites it
111 citing papers in PubMed, 200 citations in OpenAlex.
- Accuracy and tolerability of self-sampling of capillary blood for analysis of inflammation and autoantibodies in rheumatoid arthritis patients-results from a randomized controlled trial.Arthritis research & therapy · 2022Trial
- Proteomic Approaches to Defining Remission and the Risk of Relapse in Rheumatoid Arthritis.Frontiers in immunology · 2021Trial
- Single-Cell Analysis Identifies Factors Associated with Rheumatoid Arthritis-Related Interstitial Lung Disease in Comparison with Idiopathic Pulmonary Fibrosis.Tuberculosis and respiratory diseases · 2026Article
- Targeting ferroptosis resistance in RA fibroblast-like synoviocytes.Nature reviews. Rheumatology · 2026Article
- Innate lymphoid cells in rheumatoid arthritis as mediators of pathology and resolution.Nature reviews. Rheumatology · 2026Review
- Large-scale analysis of temporal gene expression variation in peripheral blood.Nature communications · 2026Article
- Article
- Tofacitinib repairs inflammation and mitochondrial dysregulation in GM-CSF-reprogrammed RA macrophages.Cellular & molecular immunology · 2026Article
- Characteristics of CLA⁺Tregs in rheumatoid arthritis and their potential as biomarkers of treatment response.Arthritis research & therapy · 2026Article
- Emerging and underrecognized viral triggers of autoimmune inflammatory rheumatic disease flares.Nature reviews. Rheumatology · 2026Review
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- Epigenetic alterations in rheumatoid arthritis: multilayer mechanisms and translational opportunities.Frontiers in immunology · 2026Review
- Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine.Frontiers in pharmacology · 2026Review
- Novel insights into the biology of childhood arthritis- lessons learned from the synovium.Arthritis research & therapy · 2025Review
- Immune-cell profiling to guide stratification and treatment of patients with rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- Clinical application of single-cell RNA sequencing in disease and therapy.Clinical and translational medicine · 2025Review
- Progression to rheumatoid arthritis in at-risk individuals is defined by systemic inflammation and by T and B cell dysregulation.Science translational medicine · 2025Article
- Characterization of fibroblast-like synoviocytes from the synovial fluid of patients affected by juvenile idiopathic arthritis.Rheumatology (Oxford, England) · 2025Article
- Current state and future directions of basic research in rheumatoid arthritis.Journal of rheumatic diseases · 2025Review
- Unveiling the Therapeutic Potential: Targeting Fibroblast-like Synoviocytes in Rheumatoid Arthritis.Expert reviews in molecular medicine · 2025Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Dana E OrangeFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).ORCID 0000-0001-9859-7199
Vicky YaoFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Kirsty SawickaFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
John FakFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Mayu O FrankFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Salina ParveenFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Nathalie E BlachereFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Caryn HaleFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Fan ZhangFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Soumya RaychaudhuriFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Olga G TroyanskayaFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Robert B DarnellFrom the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
Howard Hughes Medical Institute · USBrigham and Women's Hospital · USBroad Institute · USHospital for Special Surgery · US
Funding
New York Center for Collaborative Research In Common Disease Genomics: Genome Aggregation and Joint Variant Calling for CCDG Freeze2UM1HG008901 · NHGRI · NEW YORK GENOME CENTER · PI MANIATIS, THOMAS P, WIGLER, MICHAEL H · 2016 to 2020
$56.6MDeveloping, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MTransforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8MQuantitavie and Computational Biology Graduate ProgramT32HG003284 · NHGRI · PRINCETON UNIVERSITY · PI Joshua Michael Akey, Stanislav Y. Shvartsman · 2004 to 2026
$9.9MCombining New Molecular and Informatic Strategies to Find Hidden Ways to Treat Brain DiseaseR35NS097404 · NINDS · ROCKEFELLER UNIVERSITY · PI DARNELL, ROBERT B · 2017 to 2024
$9.0Mlntegration and Visualization of Diverse Biological DataR01GM071966 · NIGMS · PRINCETON UNIVERSITY · PI TROYANSKAYA, OLGA G · 2005 to 2022
$6.4MNEUROLOGY AND THE MOLECULAR ROLE OF N-RBPS IN THE BRAINR01NS034389 · NINDS · ROCKEFELLER UNIVERSITY · PI DARNELL, ROBERT B · 1995 to 2016
$6.3MMapping the mechanisms of protein synthesis-dependent synaptic plasticityR01NS081706 · NINDS · ROCKEFELLER UNIVERSITY · PI DARNELL, ROBERT B · 2012 to 2016
$5.3MRA-SLE Molecular Deconstruction Leadership CenterUH2AR067677 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2014 to 2020
$4.3MFunctionally specialized components of disease heritability in ENCODE dataU01HG009379 · NHGRI · HARVARD SCHOOL OF PUBLIC HEALTH · PI PRICE, ALKES L, RAYCHAUDHURI, SOUMYA · 2017 to 2021
$2.5MNeurology and the molecular role of N-RBPs in the brainR56NS034389 · NINDS · ROCKEFELLER UNIVERSITY · PI DARNELL, ROBERT B · 2012 to 2012
$590kAmerican College of Rheumatology Research and Education Foundation Bridge Funding AwardMedical Research Council MR/R013926/1NCATS NIH HHS UL1 TR000043NCATS NIH HHS UL1 TR001866NHGRI NIH HHS T32 HG003284NHGRI NIH HHS U01 HG009379NHGRI NIH HHS UM1 HG008901NIAMS NIH HHS UH2 AR067677NIGMS NIH HHS R01 GM071966NIH HHS 1UM1HG008901NIH HHS NS034389NIH HHS NS081706NIH HHS NS097404NIH HHS U01 HG009379NIH HHS UH2AR067677NINDS NIH HHS R01 NS034389NINDS NIH HHS R01 NS081706NINDS NIH HHS R35 NS097404NINDS NIH HHS R56 NS034389Robertson Foundation Robertson Therapeutic Development FundSimons Foundation SFARI 240432
Abstract
backgroundRheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown.
methodsWe established a clinical and technical protocol for repeated home collection of blood in patients with rheumatoid arthritis to allow for longitudinal RNA sequencing (RNA-seq). Specimens were obtained from 364 time points during eight flares over a period of 4 years in our index patient, as well as from 235 time points during flares in three additional patients. We identified transcripts that were differentially expressed before flares and compared these with data from synovial single-cell RNA-seq. Flow cytometry and sorted-blood-cell RNA-seq in additional patients were used to validate the findings.
resultsConsistent changes were observed in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. B-cell activation was followed by expansion of circulating CD45-CD31-PDPN+ preinflammatory mesenchymal, or PRIME, cells in the blood from patients with rheumatoid arthritis; these cells shared features of inflammatory synovial fibroblasts. Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in 19 additional patients with rheumatoid arthritis.
conclusionsLongitudinal genomic analysis of rheumatoid arthritis flares revealed PRIME cells in the blood during the period before a flare and suggested a model in which these cells become activated by B cells in the weeks before a flare and subsequently migrate out of the blood into the synovium. (Funded by the National Institutes of Health and others.).
Indexed as
Gene ExpressionMesenchymal Stem CellsAdultArthritis, RheumatoidB-LymphocytesFemaleFibroblastsFlow CytometryHumansMaleMiddle AgedPatient AcuitySequence Analysis, RNASurveys and QuestionnairesSymptom Flare UpSynovial Fluid
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NCT02051114ClinicalTrials.gov
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