Comparative Proteomics Analysis of Serum Exosomes Reveals Distinct Infection Profiles and Potential Biomarkers for Pediatric Tuberculosis.

OBJECTIVE: The primary objective of the study was to investigate the proteomic content of serum exosomes from pediatric patients with and without tuberculosis (TB), with the aim of exploring the compositional variability and identifying potential biomarkers for the early diagnosis of TB in children. METHODS: This prospective study, conducted between 2021 and 2023, analyzed the exosomal proteome of sera of children with pulmonary tuberculosis (TB), extrapulmonary TB, household contacts of TB patients, and healthy controls using Sequential Window Acquisition of All Theoretical Fragment-ion Spectra Mass Spectrometry (SWATH-MS), a data-independent acquisition proteomics platform. Differentially expressed proteins were identified through statistical analyses, followed by functional enrichment analysis using bioinformatics tools to characterize the biological pathways and molecular processes associated with different clinical groups. RESULTS: A total of 325 proteins were identified, of which 15, 9, and 18 proteins were significantly altered in exosomes from pediatric patients with pulmonary TB, extrapulmonary TB and children in contact with TB patients compared to healthy children, respectively. Pediatric patients with pulmonary TB exhibited several exclusively significantly expressed proteins, including pregnancy zone protein (PZP). The significantly altered proteins of pediatric patients with pulmonary TB were most enriched in the p53 signaling pathway, while African trypanosomiasis and complement and coagulation cascade pathways were most enriched by the significantly altered proteins of pediatric extrapulmonary TB patients and children in contact with TB patients. CONCLUSIONS: Distinct protein signatures in exomes can differentiate pediatric patients with pulmonary and extrapulmonary TB, and children with household tuberculosis contact from healthy children.