Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia

作者：Yi Wang, Xiaolan Huang, Fang Li, Xinbei Jia, Nan Jia, Jin Fu, Shuang Liu, Jin Zhang, Haiyan Ge, Siyuan Huang, Yi Hui, Chunrong Sun, Fei Xiao, Xiaodai Cui, Laurence Don Wai Luu, Dong Qu, Jieqiong Li, Jun Tai · 发表于：Critical Care · 年份：2023 · DOI：10.1186/s13054-023-04378-w · 被引用次数：53 · 研究领域：Metabolomics and Mass Spectrometry Studies、Pneumonia and Respiratory Infections、Immune cells in cancer

OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycoly...