A Comprehensive Single-cell Synovial Cell Atlas from AMP Phase II Rheumatoid Arthritis

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 II, Alessandra Nerviani, Myles J. Lewis, Felice Rivellese, Costantino Pitzalis, Laura B. Hughes, Diane Horowitz, Edward DiCarlo, Ellen M. Gravallese, Brendan F. Boyce, Accelerating Medicines Partnership: RA/SLE Network, 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, Soumya Raychaudhuri

Nature 2023. doi: 10.1038/s41586-023-06708-y


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

View the data

On this website, we provide interactive data browsers to view all of the transcriptomics data for each of the manually curated cell clusters.

Contact us

Please contact us (Fan Zhang: fzhang.combio@gmail.com) with any questions or comments.

The data presented here comes from the laboratory of Dr. Soumya Raychaudhuri.