Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

引用：Zhang F, Zhang F, Jonsson AH, Nathan A, Millard N, Curtis M, Xiao Q, Gutierrez-Arcelus M, Apruzzese W, Watts GFM, Weisenfeld D, Nayar S, Rangel-Moreno J, Meednu N, Marks KE, Mantel I, Kang JB, Rumker L, Mears J, Slowikowski K, Weinand K, Orange DE, Geraldino-Pardilla L, Deane KD, Tabechian D, Ceponis A, Firestein GS, Maybury M, Sahbudin I, Ben-Artzi A, Mandelin AM, Nerviani A, Lewis MJ, Rivellese F, Pitzalis C, Hughes LB, Horowitz D, DiCarlo E, Gravallese EM, Boyce BF, Accelerating Medicines Partnership: RA/SLE Network, Moreland LW, Goodman SM, Perlman H, Holers VM, Liao KP, Filer A, Bykerk VP, Wei K, Rao DA, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. (2023). Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature. PMID 37938773 · PMC10651487 · DOI 10.1038/s41586-023-06708-y

证据类型：PRIMARY_RESEARCH

主题：single-cell

被引次数（采集时）：362

原始记录：[Europe PMC](https://europepmc.org/article/MED/37938773)

来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

作者摘要（按来源许可复用）

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.

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