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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
Anna Helena Jonsson
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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
Kevin Wei
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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
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
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
William Apruzzese
8Accelerating Medicines Partnership® Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP® RA/SLE) Network
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
Dana Weisenfeld
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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
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
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
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
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
Dana E. Orange
11Hospital for Special Surgery, New York, NY, USA
12Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, NY, USA
Javier Rangel-Moreno
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
Laura Geraldino-Pardilla
14Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA
Kevin D. Deane
15Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
Darren Tabechian
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
Arnold Ceponis
16Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA
Gary S. Firestein
16Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA
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
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
Ami Ben-Artzi
18Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Arthur M. Mandelin II
19Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Alessandra Nerviani
20Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London; London, UK
Felice Rivellese
20Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London; London, UK
Costantino Pitzalis
20Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London; London, UK
Laura B. Hughes
21Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
Diane Horowitz
22Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA
Edward DiCarlo
23Department of Pathology and Laboratory Medicine, Hospital for Special Surgery; New York, NY, USA
Ellen M. Gravallese
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Brendan F. Boyce
24Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
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
Susan M. Goodman
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
Harris Perlman
19Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
V. Michael Holers
15Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
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
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
Vivian P. Bykerk
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
Deepak A. Rao
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Laura T. Donlin
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
Jennifer H. Anolik
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
Michael B. Brenner
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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
Jennifer Albrecht
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
Jennifer L. Barnas
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
Joan M. Bathon
14Division of Rheumatology, Columbia University College of Physicians and Surgeons, New York, NY, USA
David L. Boyle
16Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA
S. Louis Bridges Jr.
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
Debbie Campbell
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
Hayley L. Carr
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
Adam Chicoine
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Andrew Cordle
29Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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
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
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
Peter K. Gregersen
22Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA
Joel M. Guthridge
32Department of Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA
Lionel B. Ivashkiv
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
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
Judith A. James
32Department of Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA
Gregory Keras
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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
Amit Lakhanpal
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
James A. Lederer
34Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Zhihan J. Li
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Yuhong Li
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Andrew McDavid
35Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry; Rochester, NY, USA
Nida Meednu
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
Ian Mantel
11Hospital for Special Surgery, New York, NY, USA
26Weill Cornell Medicine, New York, NY, USA
Mandy J. McGeachy
25Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine; Pittsburgh, PA, USA
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
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
Christopher Ritchlin
13Division of Allergy, Immunology and Rheumatology; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
William H. Robinson
36Division of Immunology and Rheumatology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA
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
Jennifer A. Seifert
15Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA
Melanie H. Smith
11Hospital for Special Surgery, New York, NY, USA
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
Paul J. Utz
36Division of Immunology and Rheumatology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA
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
Zhu Zhu
1Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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
Copyright
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.
Posted February 28, 2022.
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
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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