A consensus blood transcriptomic framework for sepsis

作者：Brendon P. Scicluna, Kiki Cano-Gamez, Katie L. Burnham, Emma E. Davenport, A. R. Moore, Soumen Khan, Charles Hinds, Olaf L. Cremer, Purvesh Khatri, Timothy E. Sweeney, Julian C. Knight, Tom van der Poll · 发表于：Nature Medicine · 年份：2025 · DOI：10.1038/s41591-025-03964-5 · 被引用次数：37 · 研究领域：Sepsis Diagnosis and Treatment、Metabolomics and Mass Spectrometry Studies、Immune Response and Inflammation

Sepsis is a life-threatening condition driven by a maladaptive host response to infection. To establish a standardized blood transcriptomic subtype model, we aggregated blood transcriptomics data from two major sepsis cohorts: the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) project (n = 678 sampled on intensive care unit admission; ClinicalTrials.gov registration no. NCT01905033 ) and the Genomic Advances in Sepsis (GAinS) study (n = 444 sampled on intensive care unit admission and n = 817 follow-up samples; ClinicalTrials.gov registration no. NCT00131196 ). We demonstrate a strong interconnection across three separate classification methods, resulting in the proposed groupings of three consensus transcriptomic subtypes (CTSs). The distinguishing characteristics of CTS1 included gene activation of typical inflammatory pathways, more pronounced endothelial activation and an overall immature neutrophil theme. CTS2 was characterized by gene activation of a heme metabolism pathway, fibrinolytic disturbances and platelet and eosinophil signatures. CTS3 was associated with genes involved in the activation of allograft rejection, interferon signaling and anticoagulation functions, together with lymphocyte and nonclassical monocyte features. Evaluating CTS classification in independent patient cohorts, specifically the vasopressin vs noradrenaline as initial therapy in septic shock (VANISH) randomized controlled trial (n = 176; ISRCTN registration no. ISRCTN20769191 ...