دورية أكاديمية
Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.
| العنوان: | Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. |
|---|---|
| المؤلفون: | Zhang F; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Rheumatology and the Center for Health Artificial Intelligence, University of Colorado School of Medicine, Aurora, CO, USA., Jonsson AH; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA., Nathan A; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Millard N; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Curtis M; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Xiao Q; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Gutierrez-Arcelus M; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Immunology, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Apruzzese W; Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Bethesda, MD, USA., Watts GFM; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Weisenfeld D; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Nayar S; Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.; Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK., Rangel-Moreno J; Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA., Meednu N; Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA., Marks KE; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Mantel I; Hospital for Special Surgery, New York, NY, USA.; Weill Cornell Medicine, New York, NY, USA., Kang JB; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Rumker L; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Mears J; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Slowikowski K; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA., Weinand K; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Orange DE; Hospital for Special Surgery, New York, NY, USA.; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, NY, USA., Geraldino-Pardilla L; Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA., Deane KD; Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA., Tabechian D; Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA., Ceponis A; Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA., Firestein GS; Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA., Maybury M; Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.; NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK., Sahbudin I; Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.; NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK., Ben-Artzi A; Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Mandelin AM 2nd; Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Nerviani A; Centre for Experimental Medicine and Rheumatology, EULAR Centre of Excellence, William Harvey Research Institute, Queen Mary University of London, London, UK.; Barts Health NHS Trust, Barts Biomedical Research Centre (BRC), National Institute for Health and Care Research (NIHR), London, UK., Lewis MJ; Centre for Experimental Medicine and Rheumatology, EULAR Centre of Excellence, William Harvey Research Institute, Queen Mary University of London, London, UK.; Barts Health NHS Trust, Barts Biomedical Research Centre (BRC), National Institute for Health and Care Research (NIHR), London, UK., Rivellese F; Centre for Experimental Medicine and Rheumatology, EULAR Centre of Excellence, William Harvey Research Institute, Queen Mary University of London, London, UK.; Barts Health NHS Trust, Barts Biomedical Research Centre (BRC), National Institute for Health and Care Research (NIHR), London, UK., Pitzalis C; Centre for Experimental Medicine and Rheumatology, EULAR Centre of Excellence, William Harvey Research Institute, Queen Mary University of London, London, UK.; Barts Health NHS Trust, Barts Biomedical Research Centre (BRC), National Institute for Health and Care Research (NIHR), London, UK.; Department of Biomedical Sciences, Humanitas University and Humanitas Research Hospital, Milan, Italy., Hughes LB; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Horowitz D; Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA., DiCarlo E; Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY, USA., Gravallese EM; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Boyce BF; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA., Moreland LW; Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.; Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Goodman SM; Hospital for Special Surgery, New York, NY, USA.; Weill Cornell Medicine, New York, NY, USA., Perlman H; Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Holers VM; Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA., Liao KP; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Filer A; Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, Birmingham, UK.; Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK.; NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK., Bykerk VP; Hospital for Special Surgery, New York, NY, USA.; Weill Cornell Medicine, New York, NY, USA., Wei K; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Rao DA; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Donlin LT; Hospital for Special Surgery, New York, NY, USA.; Weill Cornell Medicine, New York, NY, USA., Anolik JH; Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA., Brenner MB; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Raychaudhuri S; Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA. soumya@broadinstitute.org.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.; Broad Institute of MIT and Harvard, Cambridge, MA, USA. soumya@broadinstitute.org. |
| مؤلفون مشاركون: | Accelerating Medicines Partnership: RA/SLE Network |
| المصدر: | Nature [Nature] 2023 Nov; Vol. 623 (7987), pp. 616-624. Date of Electronic Publication: 2023 Nov 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
| مواضيع طبية MeSH: | Arthritis, Rheumatoid*/complications , Arthritis, Rheumatoid*/genetics , Arthritis, Rheumatoid*/immunology , Arthritis, Rheumatoid*/pathology, Humans ; Cytokines/metabolism ; Inflammation/complications ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/pathology ; Synovial Membrane/pathology ; T-Lymphocytes/immunology ; B-Lymphocytes/immunology ; Genetic Predisposition to Disease/genetics ; Phenotype ; Single-Cell Gene Expression Analysis |
| مستخلص: | Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction 1 . There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity 1,2 . Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis. We used multi-modal single-cell RNA-sequencing and surface protein data coupled with histology of synovial tissue from 79 donors to build single-cell atlas of rheumatoid arthritis synovial tissue that includes more than 314,000 cells. We stratified tissues into six groups, referred to as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched cell states. These CTAPs demonstrate the diversity of synovial inflammation in rheumatoid arthritis, ranging from samples enriched for T and B cells to those largely lacking lymphocytes. Disease-relevant cell states, cytokines, risk genes, histology and serology metrics are associated with particular CTAPs. CTAPs are dynamic and can predict treatment response, highlighting the clinical utility of classifying rheumatoid arthritis synovial phenotypes. This comprehensive atlas and molecular, tissue-based stratification of rheumatoid arthritis synovial tissue reveal new insights into rheumatoid arthritis pathology and heterogeneity that could inform novel targeted treatments. (© 2023. The Author(s).) |
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| معلومات مُعتمدة: | P01 AI148102 United States AI NIAID NIH HHS; UH2 AR067685 United States AR NIAMS NIH HHS; MR/M007669/1 United Kingdom MRC_ Medical Research Council; UH2 AR067681 United States AR NIAMS NIH HHS; UH2 AR067694 United States AR NIAMS NIH HHS; K08 AR077037 United States AR NIAMS NIH HHS; R01 AI148435 United States AI NIAID NIH HHS; UH2 AR067679 United States AR NIAMS NIH HHS; UM2 AR067678 United States AR NIAMS NIH HHS; P30 AR069655 United States AR NIAMS NIH HHS; R21 AR071670 United States AR NIAMS NIH HHS; K08 AR081412 United States AR NIAMS NIH HHS; T32 AR007258 United States AR NIAMS NIH HHS; UL1 TR001866 United States TR NCATS NIH HHS; P30 AR070253 United States AR NIAMS NIH HHS; R01 AR073290 United States AR NIAMS NIH HHS; T32 HG002295 United States HG NHGRI NIH HHS; T32 GM007753 United States GM NIGMS NIH HHS; T32 AR007530 United States AR NIAMS NIH HHS; R01 AR073833 United States AR NIAMS NIH HHS; UH2 AR067688 United States AR NIAMS NIH HHS; K08 AR072791 United States AR NIAMS NIH HHS; T32 GM144273 United States GM NIGMS NIH HHS; UH2 AR067689 United States AR NIAMS NIH HHS; R01 AR063759 United States AR NIAMS NIH HHS; MR/P021220/1 United Kingdom MRC_ Medical Research Council; UH2 AR067690 United States AR NIAMS NIH HHS; U01 HG009379 United States HG NHGRI NIH HHS; UH2 AR067677 United States AR NIAMS NIH HHS; UH2 AR067676 United States AR NIAMS NIH HHS; UH2 AR067691 United States AR NIAMS NIH HHS |
| فهرسة مساهمة: | Investigator: J Albrecht; JL Barnas; JM Bathon; DL Boyle; SL Bridges; D Campbell; HL Carr; A Chicoine; A Cordle; P Dunn; L Forbess; PK Gregersen; JM Guthridge; LB Ivashkiv; K Ishigaki; JA James; G Keras; I Korsunsky; A Lakhanpal; JA Lederer; ZJ Li; Y Li; A McDavid; MJ McGeachy; K Raza; Y Reshef; C Ritchlin; WH Robinson; S Sakaue; JA Seifert; A Singaraju; MH Smith; D Scheel-Toellner; PJ Utz; MH Weisman; A Wyse; Z Zhu |
| المشرفين على المادة: | 0 (Cytokines) |
| تواريخ الأحداث: | Date Created: 20231108 Date Completed: 20231122 Latest Revision: 20240525 |
| رمز التحديث: | 20240525 |
| مُعرف محوري في PubMed: | PMC10651487 |
| DOI: | 10.1038/s41586-023-06708-y |
| PMID: | 37938773 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1476-4687 |
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| DOI: | 10.1038/s41586-023-06708-y |