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通过血浆cfRNA测序同时监测孕期的免疫反应和微生物感染

Simultaneously Monitoring Immune Response and Microbial Infections during Pregnancy through Plasma cfRNA Sequencing.

作者信息

Pan Wenying, Ngo Thuy T M, Camunas-Soler Joan, Song Chun-Xiao, Kowarsky Mark, Blumenfeld Yair J, Wong Ronald J, Shaw Gary M, Stevenson David K, Quake Stephen R

机构信息

Departments of Bioengineering and Applied Physics, Stanford University, and Chan Zuckerberg Biohub, Stanford, CA.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA.

出版信息

Clin Chem. 2017 Nov;63(11):1695-1704. doi: 10.1373/clinchem.2017.273888. Epub 2017 Sep 13.

DOI:10.1373/clinchem.2017.273888
PMID:28904056
Abstract

BACKGROUND

Plasma cell-free RNA (cfRNA) encompasses a broad spectrum of RNA species that can be derived from both human cells and microbes. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods.

METHODS

We assessed several recently developed RNA-seq methods on cfRNA samples. We then analyzed the dynamic changes of both the human transcriptome and the microbiome of plasma during pregnancy from 60 women.

RESULTS

cfRNA reflects a well-orchestrated immune modulation during pregnancy: an up-regulation of antiinflammatory genes and an increased abundance of antimicrobial genes. We observed that the plasma microbiome remained relatively stable during pregnancy. The bacteria shows an increased prevalence and increased abundance at postpartum, which is likely to be associated with postpartum infection. We demonstrated that cfRNA-seq can be used to monitor viral infections. We detected a number of human pathogens in our patients, including an undiagnosed patient with a high load of human parvovirus B19 virus (B19V), which is known to be a potential cause of complications in pregnancy.

CONCLUSIONS

Plasma cfRNA-seq demonstrates the potential to simultaneously monitor immune response and microbial infections during pregnancy.

摘要

背景

血浆游离RNA(cfRNA)包含多种可源自人类细胞和微生物的RNA种类。由于cfRNA呈片段化且浓度较低,使用标准RNA测序方法对其转录组进行分析颇具挑战。

方法

我们对cfRNA样本评估了几种最近开发的RNA测序方法。然后,我们分析了60名女性孕期血浆中人类转录组和微生物组的动态变化。

结果

cfRNA反映了孕期精心编排的免疫调节:抗炎基因上调,抗菌基因丰度增加。我们观察到孕期血浆微生物组保持相对稳定。产后细菌的流行率和丰度增加,这可能与产后感染有关。我们证明cfRNA测序可用于监测病毒感染。我们在患者中检测到多种人类病原体,包括一名未确诊的人类细小病毒B19(B19V)高载量患者,已知该病毒是孕期并发症的潜在原因。

结论

血浆cfRNA测序显示了在孕期同时监测免疫反应和微生物感染的潜力。

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