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Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes
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 ce...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651487/ https://www.ncbi.nlm.nih.gov/pubmed/37938773 http://dx.doi.org/10.1038/s41586-023-06708-y |
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author | Zhang, Fan Jonsson, Anna Helena Nathan, Aparna Millard, Nghia Curtis, Michelle Xiao, Qian Gutierrez-Arcelus, Maria Apruzzese, William Watts, Gerald F. M. Weisenfeld, Dana Nayar, Saba Rangel-Moreno, Javier Meednu, Nida Marks, Kathryne E. Mantel, Ian Kang, Joyce B. Rumker, Laurie Mears, Joseph Slowikowski, Kamil Weinand, Kathryn Orange, Dana E. Geraldino-Pardilla, Laura Deane, Kevin D. Tabechian, Darren Ceponis, Arnoldas Firestein, Gary S. Maybury, Mark Sahbudin, Ilfita Ben-Artzi, Ami Mandelin, Arthur M. Nerviani, Alessandra Lewis, Myles J. Rivellese, Felice Pitzalis, Costantino Hughes, Laura B. Horowitz, Diane DiCarlo, Edward Gravallese, Ellen M. Boyce, Brendan F. Moreland, Larry W. Goodman, Susan M. Perlman, Harris Holers, V. Michael Liao, Katherine P. Filer, Andrew Bykerk, Vivian P. Wei, Kevin Rao, Deepak A. Donlin, Laura T. Anolik, Jennifer H. Brenner, Michael B. Raychaudhuri, Soumya |
author_facet | Zhang, Fan Jonsson, Anna Helena Nathan, Aparna Millard, Nghia Curtis, Michelle Xiao, Qian Gutierrez-Arcelus, Maria Apruzzese, William Watts, Gerald F. M. Weisenfeld, Dana Nayar, Saba Rangel-Moreno, Javier Meednu, Nida Marks, Kathryne E. Mantel, Ian Kang, Joyce B. Rumker, Laurie Mears, Joseph Slowikowski, Kamil Weinand, Kathryn Orange, Dana E. Geraldino-Pardilla, Laura Deane, Kevin D. Tabechian, Darren Ceponis, Arnoldas Firestein, Gary S. Maybury, Mark Sahbudin, Ilfita Ben-Artzi, Ami Mandelin, Arthur M. Nerviani, Alessandra Lewis, Myles J. Rivellese, Felice Pitzalis, Costantino Hughes, Laura B. Horowitz, Diane DiCarlo, Edward Gravallese, Ellen M. Boyce, Brendan F. Moreland, Larry W. Goodman, Susan M. Perlman, Harris Holers, V. Michael Liao, Katherine P. Filer, Andrew Bykerk, Vivian P. Wei, Kevin Rao, Deepak A. Donlin, Laura T. Anolik, Jennifer H. Brenner, Michael B. Raychaudhuri, Soumya |
author_sort | Zhang, Fan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10651487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106514872023-11-08 Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes Zhang, Fan Jonsson, Anna Helena Nathan, Aparna Millard, Nghia Curtis, Michelle Xiao, Qian Gutierrez-Arcelus, Maria Apruzzese, William Watts, Gerald F. M. Weisenfeld, Dana Nayar, Saba Rangel-Moreno, Javier Meednu, Nida Marks, Kathryne E. Mantel, Ian Kang, Joyce B. Rumker, Laurie Mears, Joseph Slowikowski, Kamil Weinand, Kathryn Orange, Dana E. Geraldino-Pardilla, Laura Deane, Kevin D. Tabechian, Darren Ceponis, Arnoldas Firestein, Gary S. Maybury, Mark Sahbudin, Ilfita Ben-Artzi, Ami Mandelin, Arthur M. Nerviani, Alessandra Lewis, Myles J. Rivellese, Felice Pitzalis, Costantino Hughes, Laura B. Horowitz, Diane DiCarlo, Edward Gravallese, Ellen M. Boyce, Brendan F. Moreland, Larry W. Goodman, Susan M. Perlman, Harris Holers, V. Michael Liao, Katherine P. Filer, Andrew Bykerk, Vivian P. Wei, Kevin Rao, Deepak A. Donlin, Laura T. Anolik, Jennifer H. Brenner, Michael B. Raychaudhuri, Soumya Nature Article 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. Nature Publishing Group UK 2023-11-08 2023 /pmc/articles/PMC10651487/ /pubmed/37938773 http://dx.doi.org/10.1038/s41586-023-06708-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Fan Jonsson, Anna Helena Nathan, Aparna Millard, Nghia Curtis, Michelle Xiao, Qian Gutierrez-Arcelus, Maria Apruzzese, William Watts, Gerald F. M. Weisenfeld, Dana Nayar, Saba Rangel-Moreno, Javier Meednu, Nida Marks, Kathryne E. Mantel, Ian Kang, Joyce B. Rumker, Laurie Mears, Joseph Slowikowski, Kamil Weinand, Kathryn Orange, Dana E. Geraldino-Pardilla, Laura Deane, Kevin D. Tabechian, Darren Ceponis, Arnoldas Firestein, Gary S. Maybury, Mark Sahbudin, Ilfita Ben-Artzi, Ami Mandelin, Arthur M. Nerviani, Alessandra Lewis, Myles J. Rivellese, Felice Pitzalis, Costantino Hughes, Laura B. Horowitz, Diane DiCarlo, Edward Gravallese, Ellen M. Boyce, Brendan F. Moreland, Larry W. Goodman, Susan M. Perlman, Harris Holers, V. Michael Liao, Katherine P. Filer, Andrew Bykerk, Vivian P. Wei, Kevin Rao, Deepak A. Donlin, Laura T. Anolik, Jennifer H. Brenner, Michael B. Raychaudhuri, Soumya Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes |
title | Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes |
title_full | Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes |
title_fullStr | Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes |
title_full_unstemmed | Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes |
title_short | Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes |
title_sort | deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651487/ https://www.ncbi.nlm.nih.gov/pubmed/37938773 http://dx.doi.org/10.1038/s41586-023-06708-y |
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