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Cellular deconstruction of inflamed synovium defines diverse inflammatory phenotypes in rheumatoid arthritis

View ORCID ProfileFan Zhang, View ORCID ProfileAnna Helena Jonsson, View ORCID ProfileAparna Nathan, View ORCID ProfileKevin Wei, View ORCID ProfileNghia Millard, Qian Xiao, Maria Gutierrez-Arcelus, William Apruzzese, Gerald F. M. Watts, Dana Weisenfeld, View ORCID ProfileJoyce B. Kang, View ORCID ProfileLaurie Rumker, Joseph Mears, View ORCID ProfileKamil Slowikowski, View ORCID ProfileKathryn Weinand, View ORCID ProfileDana E. Orange, Javier Rangel-Moreno, Laura Geraldino-Pardilla, Kevin D. Deane, Darren Tabechian, Arnold Ceponis, Gary S. Firestein, Mark Maybury, Ilfita Sahbudin, Ami Ben-Artzi, Arthur M. Mandelin II, Alessandra Nerviani, Felice Rivellese, Costantino Pitzalis, Laura B. Hughes, Diane Horowitz, Edward DiCarlo, Ellen M. Gravallese, Brendan F. Boyce, Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Larry W. Moreland, Susan M. Goodman, Harris Perlman, V. Michael Holers, View ORCID ProfileKatherine P. Liao, Andrew Filer, Vivian P. Bykerk, View ORCID ProfileDeepak A. Rao, View ORCID ProfileLaura T. Donlin, View ORCID ProfileJennifer H. Anolik, View ORCID ProfileMichael B. Brenner, View ORCID ProfileSoumya Raychaudhuri, Jennifer Albrecht, Jennifer L. Barnas, Joan M. Bathon, David L. Boyle, S. Louis Bridges Jr., Debbie Campbell, Hayley L. Carr, Adam Chicoine, Andrew Cordle, Michelle Curtis, Patrick Dunn, Lindsy Forbess, Peter K. Gregersen, Joel M. Guthridge, Lionel B. Ivashkiv, Kazuyoshi Ishigaki, Judith A. James, Gregory Keras, Ilya Korsunsky, Amit Lakhanpal, James A. Lederer, Zhihan J. Li, Yuhong Li, Andrew McDavid, Nida Meednu, Ian Mantel, Mandy J. McGeachy, Karim Raza, Yakir Reshef, Christopher Ritchlin, William H. Robinson, Saori Sakaue, Jennifer A. Seifert, Melanie H. Smith, Dagmar Scheel-Toellner, Paul J. Utz, Michael H. Weisman, Zhu Zhu
doi: https://doi.org/10.1101/2022.02.25.481990
Fan Zhang
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Division of Rheumatology and the Center for Health Artificial Intelligence, University of Colorado School of Medicine, Aurora, CO, USA
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  • ORCID record for Fan Zhang
Anna Helena Jonsson
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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  • ORCID record for Anna Helena Jonsson
Aparna Nathan
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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  • ORCID record for Aparna Nathan
Kevin Wei
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Nghia Millard
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Qian Xiao
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Maria Gutierrez-Arcelus
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
7Division of Immunology, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA. US
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William Apruzzese
8Accelerating Medicines Partnership® Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP® RA/SLE) Network
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Gerald F. M. Watts
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Dana Weisenfeld
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Joyce B. Kang
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Laurie Rumker
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Joseph Mears
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Kamil Slowikowski
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
9Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA
10MGH Cancer Center, Boston, MA, USA
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Kathryn Weinand
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Dana E. Orange
11Hospital for Special Surgery, New York, NY, USA
12Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, NY, USA
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Javier Rangel-Moreno
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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Laura Geraldino-Pardilla
14Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA
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Kevin D. Deane
15Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
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Darren Tabechian
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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Arnold Ceponis
16Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA
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Gary S. Firestein
16Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA
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Mark Maybury
17Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
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Ilfita Sahbudin
17Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
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Ami Ben-Artzi
18Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Arthur M. Mandelin II
19Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Alessandra Nerviani
20Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London; London, UK
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Felice Rivellese
20Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London; London, UK
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Costantino Pitzalis
20Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London; London, UK
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Laura B. Hughes
21Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Diane Horowitz
22Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA
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Edward DiCarlo
23Department of Pathology and Laboratory Medicine, Hospital for Special Surgery; New York, NY, USA
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Ellen M. Gravallese
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Brendan F. Boyce
24Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
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Larry W. Moreland
15Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
25Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Pittsburgh, PA, USA
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Susan M. Goodman
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
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Harris Perlman
19Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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V. Michael Holers
15Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
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Katherine P. Liao
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
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Andrew Filer
17Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
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Vivian P. Bykerk
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
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Deepak A. Rao
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Laura T. Donlin
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
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Jennifer H. Anolik
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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Michael B. Brenner
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Soumya Raychaudhuri
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
27Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
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  • For correspondence: soumya@broadinstitute.org
Jennifer Albrecht
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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Jennifer L. Barnas
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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14Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA
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16Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA
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S. Louis Bridges Jr.
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
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13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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17Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
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Adam Chicoine
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Andrew Cordle
29Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Michelle Curtis
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Patrick Dunn
30Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
31Northrop Grumman Health Solutions, Rockville, MD, USA
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Lindsy Forbess
17Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
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22Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA
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Joel M. Guthridge
32Department of Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA
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Lionel B. Ivashkiv
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
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Kazuyoshi Ishigaki
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
33Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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Judith A. James
32Department of Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA
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Gregory Keras
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Ilya Korsunsky
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Amit Lakhanpal
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
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James A. Lederer
34Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Zhihan J. Li
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Yuhong Li
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Andrew McDavid
35Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry; Rochester, NY, USA
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Nida Meednu
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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Ian Mantel
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
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Mandy J. McGeachy
25Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Pittsburgh, PA, USA
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Karim Raza
17Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
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Yakir Reshef
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Christopher Ritchlin
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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William H. Robinson
36Division of Immunology and Rheumatology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA
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Saori Sakaue
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Jennifer A. Seifert
15Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
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Melanie H. Smith
11Hospital for Special Surgery, New York, NY, USA
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Dagmar Scheel-Toellner
17Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
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Paul J. Utz
36Division of Immunology and Rheumatology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA
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Michael H. Weisman
18Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
36Division of Immunology and Rheumatology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA
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Zhu Zhu
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Summary

Rheumatoid arthritis (RA) is a prototypical autoimmune disease that causes destructive tissue inflammation in joints and elsewhere. Clinical challenges in RA include the empirical selection of drugs to treat patients, inadequate responders with incomplete disease remission, and lack of a cure. We profiled the full spectrum of cells in inflamed synovium from patients with RA with the goal of deconstructing the cell states and pathways characterizing pathogenic heterogeneity in RA. Our multicenter consortium effort used multi-modal CITE-seq, RNA-seq, and histology of synovial tissue from 79 donors to build a >314,000 single-cell RA synovial cell atlas with 77 cell states from T, B/plasma, natural killer, myeloid, stromal, and endothelial cells. We stratified tissue samples into six distinct cell type abundance phenotypes (CTAPs) individually enriched for specific cell states. These CTAPs demonstrate the striking diversity of RA synovial inflammation, ranging from marked enrichment of T and B cells (CTAP-TB) to a congregation of specific myeloid, fibroblast, and endothelial cells largely lacking lymphocytes (CTAP-EFM). Disease-relevant cytokines, histology, and serology metrics are associated with certain CTAPs. This comprehensive RA synovial atlas and molecular, tissue-based CTAP stratification reveal new insights into RA pathology and heterogeneity, which could lead to novel targeted-treatment approaches in RA.

Competing Interest Statement

A.H.J. reports research support from Amgen, outside the submitted work. K.W. is a consultant for Mestag Therapeutics and Gilead Sciences and reports grant support from Gilead Sciences. S.M.G. reports research support from Novartis and is a consultant for UCB, outside the submitted work. V.M.H. is a co-founder of Q32 Bio and has previously received sponsored research from Janssen and been a consultant for Celgene and BMS, outside the submitted work. A.F. reports personal fees from Abbvie, Roche, and Janssen and grant support from Roche, UCB, Nascient, Mestag, GlaxoSmithKline, and Janssen, outside the submitted work. D.A.R. reports personal fees from Pfizer, Janssen, Merck, Scipher Medicine, GlaxoSmithKline, and Bristol-Myers Squibb and grant support from Janssen and Bristol-Myers Squibb, outside the submitted work. In addition, D.A.R. is a co-inventor on a patent submitted on T peripheral helper cells. M.B.B. is a founder for Mestag Therapeutics and a consultant for GlaxoSmithKline, 4FO Ventures, and Scailyte AG. S.R. is a founder for Mestag Therapeutics, a scientific advisor for Janssen and Pfizer, and a consultant for Gilead and Rheos Medicines.

Footnotes

  • ↵* These authors jointly supervised this work

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Cellular deconstruction of inflamed synovium defines diverse inflammatory phenotypes in rheumatoid arthritis
Fan Zhang, Anna Helena Jonsson, Aparna Nathan, Kevin Wei, Nghia Millard, Qian Xiao, Maria Gutierrez-Arcelus, William Apruzzese, Gerald F. M. Watts, Dana Weisenfeld, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kamil Slowikowski, Kathryn Weinand, Dana E. Orange, Javier Rangel-Moreno, Laura Geraldino-Pardilla, Kevin D. Deane, Darren Tabechian, Arnold Ceponis, Gary S. Firestein, Mark Maybury, Ilfita Sahbudin, Ami Ben-Artzi, Arthur M. Mandelin II, Alessandra Nerviani, Felice Rivellese, Costantino Pitzalis, Laura B. Hughes, Diane Horowitz, Edward DiCarlo, Ellen M. Gravallese, Brendan F. Boyce, Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Larry W. Moreland, Susan M. Goodman, Harris Perlman, V. Michael Holers, Katherine P. Liao, Andrew Filer, Vivian P. Bykerk, Deepak A. Rao, Laura T. Donlin, Jennifer H. Anolik, Michael B. Brenner, Soumya Raychaudhuri, Jennifer Albrecht, Jennifer L. Barnas, Joan M. Bathon, David L. Boyle, S. Louis Bridges Jr., Debbie Campbell, Hayley L. Carr, Adam Chicoine, Andrew Cordle, Michelle Curtis, Patrick Dunn, Lindsy Forbess, Peter K. Gregersen, Joel M. Guthridge, Lionel B. Ivashkiv, Kazuyoshi Ishigaki, Judith A. James, Gregory Keras, Ilya Korsunsky, Amit Lakhanpal, James A. Lederer, Zhihan J. Li, Yuhong Li, Andrew McDavid, Nida Meednu, Ian Mantel, Mandy J. McGeachy, Karim Raza, Yakir Reshef, Christopher Ritchlin, William H. Robinson, Saori Sakaue, Jennifer A. Seifert, Melanie H. Smith, Dagmar Scheel-Toellner, Paul J. Utz, Michael H. Weisman, Zhu Zhu
bioRxiv 2022.02.25.481990; doi: https://doi.org/10.1101/2022.02.25.481990
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Cellular deconstruction of inflamed synovium defines diverse inflammatory phenotypes in rheumatoid arthritis
Fan Zhang, Anna Helena Jonsson, Aparna Nathan, Kevin Wei, Nghia Millard, Qian Xiao, Maria Gutierrez-Arcelus, William Apruzzese, Gerald F. M. Watts, Dana Weisenfeld, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kamil Slowikowski, Kathryn Weinand, Dana E. Orange, Javier Rangel-Moreno, Laura Geraldino-Pardilla, Kevin D. Deane, Darren Tabechian, Arnold Ceponis, Gary S. Firestein, Mark Maybury, Ilfita Sahbudin, Ami Ben-Artzi, Arthur M. Mandelin II, Alessandra Nerviani, Felice Rivellese, Costantino Pitzalis, Laura B. Hughes, Diane Horowitz, Edward DiCarlo, Ellen M. Gravallese, Brendan F. Boyce, Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Larry W. Moreland, Susan M. Goodman, Harris Perlman, V. Michael Holers, Katherine P. Liao, Andrew Filer, Vivian P. Bykerk, Deepak A. Rao, Laura T. Donlin, Jennifer H. Anolik, Michael B. Brenner, Soumya Raychaudhuri, Jennifer Albrecht, Jennifer L. Barnas, Joan M. Bathon, David L. Boyle, S. Louis Bridges Jr., Debbie Campbell, Hayley L. Carr, Adam Chicoine, Andrew Cordle, Michelle Curtis, Patrick Dunn, Lindsy Forbess, Peter K. Gregersen, Joel M. Guthridge, Lionel B. Ivashkiv, Kazuyoshi Ishigaki, Judith A. James, Gregory Keras, Ilya Korsunsky, Amit Lakhanpal, James A. Lederer, Zhihan J. Li, Yuhong Li, Andrew McDavid, Nida Meednu, Ian Mantel, Mandy J. McGeachy, Karim Raza, Yakir Reshef, Christopher Ritchlin, William H. Robinson, Saori Sakaue, Jennifer A. Seifert, Melanie H. Smith, Dagmar Scheel-Toellner, Paul J. Utz, Michael H. Weisman, Zhu Zhu
bioRxiv 2022.02.25.481990; doi: https://doi.org/10.1101/2022.02.25.481990

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