Plasma proteomics identifies molecular subtypes in sepsis

作者：Thilo Bracht, K Käppler, Malte Bayer, Franziska Grell, Karin Schork, Lars Palmowski, Björn Koos, Tim Rahmel, Dominik Ziehe, Matthias Unterberg, Lars Bergmann, Katharina Rump, Martina Broecker‐Preuss, Ulrich Limper, Dietrich Henzler, Stefan Ehrentraut, Thilo von Groote, Alexander Zarbock, Stephanie Pfaender, Nina Babel, Katrin Marcus, Martin Eisenacher, Michael Adamzik, Barbara Sitek, Hartmuth Nowak · 发表于：Critical Care · 年份：2025 · DOI：10.1186/s13054-025-05639-6 · 被引用次数：17 · 研究领域：Sepsis Diagnosis and Treatment、Advanced Proteomics Techniques and Applications、Neonatal and Maternal Infections

BACKGROUND: The heterogeneity of sepsis represents a significant challenge to the development of personalized sepsis therapies. Sepsis subtyping has therefore emerged as an important approach to this problem, but its impact on clinical practice was limited due to insufficient molecular insights. Modern proteomics techniques allow the identification of subtypes and provide molecular and mechanistical insights. In this study, we analyzed a prospective multi-center sepsis cohort using plasma proteomics to describe and characterize sepsis plasma proteome subtypes. METHODS: Plasma samples were collected from 333 patients at days 1 and 4 of sepsis and analyzed using liquid chromatography coupled to tandem mass spectrometry. Plasma proteome subtypes were identified using K-means clustering and characterized based on clinical routine data, cytokine measurements, and proteomics data. A random forest machine learning classifier was generated to showcase future assignment of patients to subtypes. RESULTS: Four subtypes with different sepsis severity were identified. Cluster 0 represented the most severe form of sepsis, with 100% mortality. Cluster 1, 2 and 3 showed a gradual decrease of the median SOFA score, as reflected by clinical data and cytokine measurements. At the proteome level, the subtypes were characterized by distinct molecular features. We observed an alternating immune response, with cluster 1 showing prominent activation of the adaptive immune system, as indicated by ele...