PRIME细胞的RNA鉴定可用于预测类风湿性关节炎耀斑
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PRIME细胞的RNA鉴定可用于预测类风湿性关节炎耀斑

2020-07-18 18:48      点击:

本期文章:《新英格兰医学杂志》:Vol.383 No.3

美国洛克菲勒大学Dana E. Orange联合Robert B. Darnell团队对预测类风湿性关节炎耀斑的PRIME细胞进行了RNA鉴定。2020年7月6日,《新英格兰医学杂志》发表了这一成果。

与许多炎症性疾病一样,类风湿关节炎的特征是存在静止和恶化(耀斑)期。导致耀斑的分子机制仍未可知。

研究组为类风湿关节炎患者建立了一种临床技术方案,用于回家后多次采血,以进行纵向RNA测序(RNA-seq)。指标患者在4年的时间里,8次耀斑期间,采集了364个时间点的样本,另外3名患者采集了235个时间点的样本。研究组鉴定了在耀斑前差异表达的转录本,并将其与滑膜单细胞RNA序列数据进行了比较。用流式细胞仪和分类血细胞RNA序列对其他患者进行验证。

类风湿关节炎发作前1-2周,在血液转录谱中观察到一致的变化。B细胞活化后,类风湿关节炎患者血液中循环的CD45-CD31-PDPN +炎症前间充质细胞(PRIME)扩增。这些细胞具有炎性滑膜成纤维细胞的特征。所有4例患者在耀斑期间循环PRIME细胞的水平均下降,流式细胞仪和分类细胞RNA-seq证实了另外19名类风湿性关节炎患者中存在PRIME细胞。

类风湿性关节炎发作的纵向基因组分析揭示了在耀斑前几周,血液中的PRIME细胞被B细胞激活,随后从血液迁移到滑膜中。

附:英文原文

Title: RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares

Author: 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.

Issue&Volume: 2020-07-15

Abstract: Abstract

Background

Rheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown.

Methods

We established a clinical and technical protocol for repeated home collection of blood in patients with rheumatoid arthritis to allow for longitudinal RNA sequencing (RNA-seq). Specimens were obtained from 364 time points during eight flares over a period of 4 years in our index patient, as well as from 235 time points during flares in three additional patients. We identified transcripts that were differentially expressed before flares and compared these with data from synovial single-cell RNA-seq. Flow cytometry and sorted-blood-cell RNA-seq in additional patients were used to validate the findings.

Results

Consistent changes were observed in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. B-cell activation was followed by expansion of circulating CD45CD31PDPN+ preinflammatory mesenchymal, or PRIME, cells in the blood from patients with rheumatoid arthritis; these cells shared features of inflammatory synovial fibroblasts. Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in 19 additional patients with rheumatoid arthritis.

Conclusions

Longitudinal genomic analysis of rheumatoid arthritis flares revealed PRIME cells in the blood during the period before a flare and suggested a model in which these cells become activated by B cells in the weeks before a flare and subsequently migrate out of the blood into the synovium.

DOI: NJ202007163830309

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2004114

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
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