Quantitative proteomic characterization of microvesicles/exosomes from the cerebrospinal fluid of patients with acute bilirubin encephalopathy

Severe hyperbilirubinemia causes neurotoxicity and may lead to acute bilirubin encephalopathy (ABE) during the critical period of central nervous system development. The aim of the present study was to identify differentially expressed proteins (DEPs) in microvesicles/exosomes (MV/E) isolated from the cerebrospinal fluid (CSF) of patients with ABE. Co-precipitation was used to isolate the MV/E from the CSF of patients with ABE and age-matched controls. Isobaric tagging for relative and absolute quantification-based proteomic technology combined with liquid chromatography/tandem mass spectrometry was used to identify DEPs in the MV/E. Bioinformatics analysis was subsequently performed to investigate Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes enriched signaling pathways of these DEPs. A total of four proteins were selected for further validation via western blotting. A total of 291 dysregulated proteins were identified by comparing the patients with ABE with the controls. Bioinformatics analysis indicated the involvement of immune-inflammation-associated cellular processes and signaling pathways in the pathophysiology of ABE. In conclusion, the present study identified the proteomic profile of MV/E isolated from the CSF of patients with ABE. These results may provide an improved understanding of the pathogenesis of ABE and may help to identify early diagnostic biomarkers and therapeutic targets.