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西非脓毒症队列血液中的基因表达特征定义宿主反应表型。

Gene expression signatures in blood from a West African sepsis cohort define host response phenotypes.

机构信息

Austere environments Consortium for Enhanced Sepsis Outcomes (ACESO), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

出版信息

Nat Commun. 2024 May 30;15(1):4606. doi: 10.1038/s41467-024-48821-0.

Abstract

Our limited understanding of the pathophysiological mechanisms that operate during sepsis is an obstacle to rational treatment and clinical trial design. There is a critical lack of data from low- and middle-income countries where the sepsis burden is increased which inhibits generalized strategies for therapeutic intervention. Here we perform RNA sequencing of whole blood to investigate longitudinal host response to sepsis in a Ghanaian cohort. Data dimensional reduction reveals dynamic gene expression patterns that describe cell type-specific molecular phenotypes including a dysregulated myeloid compartment shared between sepsis and COVID-19. The gene expression signatures reported here define a landscape of host response to sepsis that supports interventions via targeting immunophenotypes to improve outcomes.

摘要

我们对脓毒症发生时病理生理机制的有限认识,是合理治疗和临床试验设计的障碍。在脓毒症负担增加的低收入和中等收入国家,缺乏关键数据,这妨碍了治疗干预的普遍策略。在这里,我们对全血进行 RNA 测序,以研究加纳队列中脓毒症的宿主反应的纵向变化。数据降维揭示了描述特定于细胞类型的分子表型的动态基因表达模式,包括脓毒症和 COVID-19 之间失调的髓系细胞。这里报告的基因表达特征定义了宿主对脓毒症反应的图谱,支持通过针对免疫表型进行干预以改善预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5b8/11139862/bd21245d83cb/41467_2024_48821_Fig1_HTML.jpg

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