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

ABSTRACT: Detailed understanding of host pathogen interaction in tuberculosis is an important avenue for identifying novel therapeutic targets. Small extracellular vesicles (EVs) like exosomes are rich in proteins, nucleic acids and lipids, act as messenger and may show altered composition in disease condition. In this case control study, we isolated small EVs from serum of 58 subjects (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 set (n=42) 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 (log2 fold change >±0.48 at p<0.05) in ATB with respect to healthy controls and Western blot data corroborated mass spectrometry findings. These important proteins involve in kynurenine metabolic pathway, neutrophil degranulation, scavenging of heme from plasma 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr. Ranjan Kumar Nanda  

PROVIDER: MSV000082412 | MassIVE | Tue May 29 02:15:00 BST 2018

SECONDARY ACCESSION(S): PXD009947

REPOSITORIES: MassIVE