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预测类风湿关节炎发作的PRIME细胞的RNA鉴定
RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares


Dana E. Orange ... 其他 • 2020.07.16
相关阅读
• 吸烟与类风湿性关节炎风险

摘要


背景

与许多炎性疾病一样,类风湿关节炎的特征是静止和加重(发作)交替出现。而导致发作的分子事件尚未明确。

 

方法

我们为类风湿关节炎患者制定了一份关于在家中反复采血的临床和技术方案,以便进行纵向的RNA测序(RNA-seq)。指示病例在4年期间8次发作中的364个时间点采集了样本,另外3例患者在发作中的235个时间点采集了样本。我们鉴定了发作前差异表达的转录物,并将这些转录物与滑膜单细胞RNA-seq的数据进行了比较。我们利用其他患者的流式细胞术和分选血细胞RNA-seq验证了这些发现。

 

结果

我们在患者类风湿关节炎发作前1~2周观察到血液转录谱有一致变化。类风湿关节炎患者出现B细胞活化,随后血液内的循环CD45-CD31-PDPN+炎症前间充质细胞(preinflammatory mesenchymal cell,PRIME细胞)扩增;这些细胞具有炎性滑膜成纤维细胞的特征。全部4例患者的循环PRIME细胞水平在发作期间均降低,而流式细胞术和分选细胞RNA-seq在另外19例类风湿关节炎患者证实存在PRIME细胞。

 

结论

对类风湿关节炎发作进行的纵向基因组分析表明,在发作前,患者血液内存在PRIME细胞,并提示了以下模型:这些细胞在发作前数周内被B细胞激活,然后从血液内迁移到滑膜内(由美国国立卫生研究院等资助)。





作者信息

Dana E. Orange, M.D., Vicky Yao, Ph.D., Kirsty Sawicka, Ph.D., John Fak, M.S., Mayu O. Frank, N.P., Ph.D., Salina Parveen, M.A., Nathalie E. Blachere, Ph.D., Caryn Hale, Ph.D., Fan Zhang, Ph.D., Soumya Raychaudhuri, M.D., Ph.D., Olga G. Troyanskaya, Ph.D., and Robert B. Darnell, M.D., Ph.D.
From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) — all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge — both in Massachusetts (F.Z., S.R.). Address reprint requests to Dr. Orange at Rockefeller University, Hospital for Special Surgery, 1230 York Ave., New York, NY 10075, or at dorange@rockefeller.edu, or to Dr. Darnell at Rockefeller University, 1230 York Ave., New York, NY 10075, or at darnelr@rockefeller.edu.

 

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