Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes

Zhang, Fan and Jonsson, Anna Helena and Nathan, Aparna and Millard, Nghia and Curtis, Michelle and Xiao, Qian and Gutierrez-Arcelus, Maria and Apruzzese, William and Watts, Gerald F. M. and Weisenfeld, Dana and Nayar, Saba and Rangel-Moreno, Javier and Meednu, Nida and Marks, Kathryne E. and Mantel, Ian and Kang, Joyce B. and Rumker, Laurie and Mears, Joseph and Slowikowski, Kamil and Weinand, Kathryn and Orange, Dana E. and Geraldino-Pardilla, Laura and Deane, Kevin D. and Tabechian, Darren and Ceponis, Arnoldas and Firestein, Gary S. and Maybury, Mark and Sahbudin, Ilfita and Ben-Artzi, Ami and Mandelin, Arthur M. and Nerviani, Alessandra and Lewis, Myles J. and Rivellese, Felice and Pitzalis, Costantino and Hughes, Laura B. and Horowitz, Diane and DiCarlo, Edward and Gravallese, Ellen M. and Boyce, Brendan F. and Albrecht, Jennifer and Barnas, Jennifer L. and Bathon, Joan M. and Boyle, David L. and Bridges, S. Louis and Campbell, Debbie and Carr, Hayley L. and Chicoine, Adam and Cordle, Andrew and Dunn, Patrick and Forbess, Lindsy and Gregersen, Peter K. and Guthridge, Joel M. and Ivashkiv, Lionel B. and Ishigaki, Kazuyoshi and James, Judith A. and Keras, Gregory and Korsunsky, Ilya and Lakhanpal, Amit and Lederer, James A. and Li, Zhihan J. and Li, Yuhong and McDavid, Andrew and McGeachy, Mandy J. and Raza, Karim and Reshef, Yakir and Ritchlin, Christopher and Robinson, William H. and Sakaue, Saori and Seifert, Jennifer A. and Singaraju, Anvita and Smith, Melanie H. and Scheel-Toellner, Dagmar and Utz, Paul J. and Weisman, Michael H. and Wyse, Aaron and Zhu, Zhu and Moreland, Larry W. and Goodman, Susan M. and Perlman, Harris and Holers, V. Michael and Liao, Katherine P. and Filer, Andrew and Bykerk, Vivian P. and Wei, Kevin and Rao, Deepak A. and Donlin, Laura T. and Anolik, Jennifer H. and Brenner, Michael B. and Raychaudhuri, Soumya (2023) Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature. ISSN 0028-0836

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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.

Item Type: Article
Subjects: GO for STM > Multidisciplinary
Depositing User: Unnamed user with email support@goforstm.com
Date Deposited: 10 Nov 2023 04:47
Last Modified: 10 Nov 2023 04:47
URI: http://archive.article4submit.com/id/eprint/2186

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