小柯机器人

美国布里格姆妇女医院和哈佛医学院Soumya Raychaudhuri团队近期取得重要工作进展，他们通过解构类风湿关节炎滑膜来定义炎症亚型。相关研究成果2023年11月8日在线发表于《自然》杂志上。

据介绍，类风湿性关节炎是一种典型的自身免疫性疾病，可引起关节炎症和破坏。目前还没有治愈类风湿性关节炎的方法，治疗的有效性因患者而异，这表明致病的多样性尚不明确。

为解构表征这种致病异质性的细胞状态和途径，研究人员对类风湿性关节炎患者发炎滑膜中的全谱细胞进行了分析。使用多模式单细胞RNA测序和表面蛋白数据，结合79名捐赠者滑膜组织的组织学，构建了包括314000多个细胞的类风湿性关节炎滑膜组织的单细胞图谱。研究人员将组织分为六组，称为细胞型丰度表型（CTAP），每一组都以选择性富集的细胞状态为特征。这些CTAP证明了类风湿性关节炎滑膜炎症的多样性，从富含T和B细胞的样本到大量缺乏淋巴细胞的样本。疾病相关的细胞状态、细胞因子、风险基因、组织学和血清学指标与特定的CTAP相关。CTAP是动态的，可以预测治疗反应，突出了对类风湿性关节炎滑膜表型进行分类的临床实用性。

总之，这一全面的图谱和基于分子、组织的类风湿性关节炎滑膜组织分层揭示了对类风湿性关节病病理学和异质性的新见解，可以为新的靶向治疗提供信息。

附：英文原文

Title: Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes

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

Issue&Volume: 2023-11-08

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. Single-cell transcriptomic and proteomic data from synovial tissue from individuals with rheumatoid arthritis classify patients into groups based on abundance of cell states that can provide insights into pathology and predict individual treatment responses.

DOI: 10.1038/s41586-023-06708-y

Source: https://www.nature.com/articles/s41586-023-06708-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html