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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

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

Arya Rakesh R Dabral Deepti D Faruquee Hossain Md HM Mazumdar Himangshu H Patgiri Saurav Jyoti SJ Deka Trinayan T Basumatary Rumi R Kupa Rukuwe-U RU Semy Chayale C Kapfo Wetetsho W Liegise Kevideme K Kaur Inderjeet I Choedon Tenzin T Kumar Purnima P Behera Rajendra Kumar RK Deori Pranjal P Nath Reema R Khalo Kerekha K Saikia Lahari L Khamo Vinotsole V Nanda Ranjan Kumar RK

Proteomics. Clinical applications 20191009 1

<h4>Purpose</h4>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.<h4>Experimental design</h4>In this case control study, small EVs are isolated from serum of 58 subjects (all male, 33 (15-70) in years) including drug naïve active tuberculos ...[more]

PMID: 31532894

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Project description:Novel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respiratory infections. We applied a highly sensitive non-depletion tandem mass spectrometry discovery approach to investigate plasma protein expression in pulmonary TB cases compared to healthy controls in South African and Peruvian cohorts. . Plasma samples were analysed from 11 untreated male patients with active pulmonary TB and 10 male healthy control samples. Each plasma sample was initially separated into four segments by size exclusion chromatography, and each segment was processed individually. Analyses of plasma segments were performed in twelve iTRAQ (isobaric tags for relative and absolute quantification) 8-plex experimental sets in a block randomised design comprising three experimental sets. Each iTRAQ experiment contained a bridging master-pool plasma sample run in every experiment. Healthy controls were matched to TB samples by age, ethnicity, and smoking status within each iTRAQ set. Protein abundances from the plasma segments and multi-consensus reports were combined and adjusted for experimental batch effects. Protein abundances from the remaining combined plasma segment proteomes between experimental sets and the combined multi-consensus proteomes were analysed by complementary bioinformatic approaches to identify candidate diagnostic protein biomarkers. In total, 4,696 protein identifications were made across all iTRAQ experiments, at 5% FDR (false discovery rate). This comprised 2,332 unique host-derived proteins and 22 Mtb-derived proteins. Of these, 594 host proteins had a quantification result for every sample analysed and therefore comprised the complete quantified proteome. Subsequent bioinformatic analysis identified 118 differentially expressed proteins by three complementary bioinformatic pipelines and were taken forward in subsequent validation work as strong candidate biomarkers of pulmonary TB.

Dataset Information

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

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

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