Serum Small Extracellular Vesicles Proteome of Tuberculosis Patients Demonstrated Deregulated Immune Response.

Detailed understanding of host pathogen interaction in tuberculosis is an important avenue for identifying novel therapeutic targets. Small extracellular vesicles (EVs) like exosomes that are rich in proteins, nucleic acids and lipids, act as messengers and may show altered composition in disease conditions.In this case control study, we isolated small EVs from serum of 58 subjects (all male, 33 (15-70) in years) including drug naïve active tuberculosis (ATB: n = 22), non-tuberculosis (NTB: n = 18) and healthy subjects (n = 18). Serum small EVs proteome analysis was carried out using isobaric tag for relative and absolute quantification (iTRAQ) experiments and an independent sample (n = 36) was used for validation.A set of 132 and 68 proteins were identified in iTRAQ-I (ATB/Healthy) and iTRAQ-II (ATB/NTB) experiments, respectively. Four proteins (KYAT3, SERPINA1, HP and APOC3) showed deregulation (log fold change >±0.48, p < 0.05) in ATB with respect to healthy controls and Western blot data corroborated mass spectrometry findings.These important proteins, involved in neutrophil degranulation, plasma heme scavenging, kynurenine and lipid metabolism, showed deregulation in ATB patients. Identification of such a protein panel in circulating small EVs besides providing novel insights into their role in tuberculosis may prove to be useful targets to develop host-directed therapeutic intervention.Although, small extracellular vesicles (EVs) proteome has been studied to understand its role in disease conditions such as tuberculosis, but the clinical significance of the marker proteins has not yet been explored. Our study provides a new insight into the serum small EVs proteome of tuberculosis patients which can be explained by change in expression of important proteins such as SERPINA1, KYAT3, HP and APOC3. These findings could be useful to understand the pathophysiological conditions in greater detail and may serve as important molecular targets to develop host directed therapeutic interventions in tuberculosis. This article is protected by copyright. All rights reserved.