Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia
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
Affiliations
Yi Wang
Experimental Research Center, Capital Institute of Pediatrics
Xiaolan Huang
Experimental Research Center, Capital Institute of Pediatrics
Fang Li
Department of Critical Medicine, Children’s Hospital Affiliated Capital Institute of Pediatrics
Xinbei Jia
Department of Otorhinolaryngology Head and Neck Surgery, Children’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College
Nan Jia
Experimental Research Center, Capital Institute of Pediatrics
Jin Fu
Experimental Research Center, Capital Institute of Pediatrics
Shuang Liu
Department of Critical Medicine, Children’s Hospital Affiliated Capital Institute of Pediatrics
Jin Zhang
Department of Critical Medicine, Children’s Hospital Affiliated Capital Institute of Pediatrics
Haiyan Ge
Department of Critical Medicine, Children’s Hospital Affiliated Capital Institute of Pediatrics
Siyuan Huang
Department of Critical Medicine, Children’s Hospital Affiliated Capital Institute of Pediatrics
Yi Hui
Department of Critical Medicine, Children’s Hospital Affiliated Capital Institute of Pediatrics
Chunrong Sun
Experimental Research Center, Capital Institute of Pediatrics
Fei Xiao
Experimental Research Center, Capital Institute of Pediatrics
Xiaodai Cui
Experimental Research Center, Capital Institute of Pediatrics
Laurence Don Wai Luu
School of Life Sciences, University of Technology Sydney
Dong Qu
Department of Critical Medicine, Children’s Hospital Affiliated Capital Institute of Pediatrics
Jieqiong Li
Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University
Jun Tai
Department of Otorhinolaryngology Head and Neck Surgery, Children’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College
Abstract 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 glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. Conclusion The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.
