Proteomic analysis of serum proteins in children with brain death

BACKGROUND: Brain death (BD) is a catastrophic physiological outcome that can occur in individuals with terminal illness and can adversely affect the graft quality after donation of their organs. As BD has no specific symptoms, it can be difficult to diagnose in a timely manner. The present study was designed to investigate the serum protein expression profiles of children affected by BD in an effort to define diagnostic biomarkers for this condition. METHODS: Blood samples were collected from 8 patients with BD and 8 healthy controls during the same time period. Tandem mass tags and mass spectrometry were used to conduct a proteomic analysis of serum extracted from the samples. The potential regulatory roles of the top 5 upregulated and downregulated proteins identified through the analysis were then explored using bioinformatics analyses and a review of the related literature. RESULTS: The top 5 upregulated proteins in the serum samples from patients with BD were lipopolysaccharide-binding protein (LBP), α1-acid glycoprotein (α1-AGP), α1-antichymotrypsin (α1-ACT), leucine-rich α1-glycoprotein (LRG1), and lactate dehydrogenase B heavy chain (LDHB), and the 5 most downregulated proteins in these samples were actin-binding protein 2 (transgelin-2), platelet basic protein (PBP), tropomyosin α4 chain (TPM4), tropomyosin α3 chain (TPM3), and peptidase inhibitor 16 (PI16). Literature searches indicated that several of the identified proteins influence the pathogeneses of various diseases, with LBP, α1-AGP, α1-ACT, LRG1, transgelin-2, and PBP all being related to inflammatory activity. CONCLUSIONS: Through a proteomics-based analysis, several differentially expressed proteins were identified in patients with BD relative to healthy controls. Most of these proteins are associated with inflammatory responses that have the potential to persist after the occurrence of BD. Further clinical work is needed to clarify the functional roles of the identified proteins.