Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes

Fan Zhang, Anna Helena Jonsson, Aparna Nathan, Nghia Millard, Michelle Curtis, Qian Xiao, Maria Gutierrez-Arcelus, William Apruzzese, Gerald F. M. Watts, Dana Weisenfeld, Saba Nayar, Javier Rangel-Moreno, Nida Meednu, Kathryne E. Marks, Ian Mantel, Joyce B. Kang, Laurie Rumker, Joseph Mears, Kamil Slowikowski, Kathryn Weinand, Dana E. Orange, Laura Geraldino-Pardilla, Kevin D. Deane, Darren Tabechian, Arnoldas Ceponis, Gary S. Firestein, Mark Maybury, Ilfita Sahbudin, Ami Ben-Artzi, Arthur M. Mandelin, Alessandra Nerviani, Myles J. Lewis, Felice Rivellese, Costantino Pitzalis, Laura B. Hughes, Diane Horowitz, Edward DiCarlo, Ellen M. Gravallese, Brendan F. Boyce, Larry W. Moreland, Susan M. Goodman, Harris Perlman, V. Michael Holers, Katherine P. Liao, Andrew Filer, Vivian P. Bykerk, Kevin Wei, Deepak A. Rao, Laura T. Donlin, Jennifer H. Anolik, Michael B. Brenner and Soumya Raychaudhuri ()
Additional contact information
Fan Zhang: Brigham and Women’s Hospital and Harvard Medical School
Anna Helena Jonsson: Brigham and Women’s Hospital and Harvard Medical School
Aparna Nathan: Brigham and Women’s Hospital and Harvard Medical School
Nghia Millard: Brigham and Women’s Hospital and Harvard Medical School
Michelle Curtis: Brigham and Women’s Hospital and Harvard Medical School
Qian Xiao: Brigham and Women’s Hospital and Harvard Medical School
Maria Gutierrez-Arcelus: Brigham and Women’s Hospital and Harvard Medical School
William Apruzzese: Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network
Gerald F. M. Watts: Brigham and Women’s Hospital and Harvard Medical School
Dana Weisenfeld: Brigham and Women’s Hospital and Harvard Medical School
Saba Nayar: University of Birmingham
Javier Rangel-Moreno: University of Rochester Medical Center
Nida Meednu: University of Rochester Medical Center
Kathryne E. Marks: Brigham and Women’s Hospital and Harvard Medical School
Ian Mantel: Hospital for Special Surgery
Joyce B. Kang: Brigham and Women’s Hospital and Harvard Medical School
Laurie Rumker: Brigham and Women’s Hospital and Harvard Medical School
Joseph Mears: Brigham and Women’s Hospital and Harvard Medical School
Kamil Slowikowski: Harvard Medical School
Kathryn Weinand: Brigham and Women’s Hospital and Harvard Medical School
Dana E. Orange: Hospital for Special Surgery
Laura Geraldino-Pardilla: Columbia University College of Physicians and Surgeons
Kevin D. Deane: University of Colorado School of Medicine
Darren Tabechian: University of Rochester Medical Center
Arnoldas Ceponis: University of California, San Diego
Gary S. Firestein: University of California, San Diego
Mark Maybury: University of Birmingham
Ilfita Sahbudin: University of Birmingham
Ami Ben-Artzi: Cedars-Sinai Medical Center
Arthur M. Mandelin: Northwestern University Feinberg School of Medicine
Alessandra Nerviani: Queen Mary University of London
Myles J. Lewis: Queen Mary University of London
Felice Rivellese: Queen Mary University of London
Costantino Pitzalis: Queen Mary University of London
Laura B. Hughes: University of Alabama at Birmingham
Diane Horowitz: Northwell Health, Manhasset
Edward DiCarlo: Hospital for Special Surgery
Ellen M. Gravallese: Brigham and Women’s Hospital and Harvard Medical School
Brendan F. Boyce: University of Rochester Medical Center
Larry W. Moreland: University of Colorado School of Medicine
Susan M. Goodman: Hospital for Special Surgery
Harris Perlman: Northwestern University Feinberg School of Medicine
V. Michael Holers: University of Colorado School of Medicine
Katherine P. Liao: Brigham and Women’s Hospital and Harvard Medical School
Andrew Filer: University of Birmingham
Vivian P. Bykerk: Hospital for Special Surgery
Kevin Wei: Brigham and Women’s Hospital and Harvard Medical School
Deepak A. Rao: Brigham and Women’s Hospital and Harvard Medical School
Laura T. Donlin: Hospital for Special Surgery
Jennifer H. Anolik: University of Rochester Medical Center
Michael B. Brenner: Brigham and Women’s Hospital and Harvard Medical School
Soumya Raychaudhuri: Brigham and Women’s Hospital and Harvard Medical School

Nature, 2023, vol. 623, issue 7987, 616-624

Abstract: Abstract Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction1. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity1,2. 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.

Date: 2023
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DOI: 10.1038/s41586-023-06708-y

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