TY - JOUR
T1 - Serum small extracellular vesicles proteome of tuberculosis patients demonstrated deregulated immune response
AU - Arya, Rakesh
AU - Dabral, Deepti
AU - Faruquee, Hossain Md.
AU - Mazumdar, Himangshu
AU - Patgiri, Saurav Jyoti
AU - Deka, Trinayan
AU - Basumatary, Rumi
AU - Kupa, Rukuwe-u
AU - Semy, Chayale
AU - Kapfo, Wetetsho
AU - Liegise, Kevideme
AU - Kaur, Inderjeet
AU - Choedon, Tenzin
AU - Kumar, Purnima
AU - Behera, Rajendra Kumar
AU - Deori, Pranjal
AU - Nath, Reema
AU - Khalo, Kerekha
AU - Saikia, Lahari
AU - Khamo, Vinotsole
AU - Nanda, Ranjan Kumar
PY - 2020
Y1 - 2020
N2 - Purpose: 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. Experimental design: 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 tuberculosis (ATB: n = 22), non-tuberculosis (NTB: n = 18), and healthy subjects (n = 18). Serum small EVs proteome analysis is carried out using isobaric tag for relative and absolute quantification (iTRAQ) experiments and an independent sample (n = 36) is used for validation. Results: A set of 132 and 68 proteins are identified in iTRAQ-I (ATB/Healthy) and iTRAQ-II (ATB/NTB) experiments, respectively. Four proteins (KYAT3, SERPINA1, HP, and APOC3) show deregulation (log2-fold change >àñ0.48, pà<à0.05) in ATB with respect to healthy controls and Western blot data corroborated mass spectrometry findings. Conclusions and clinical relevance: These important proteins, involved in neutrophil degranulation, plasma heme scavenging, kynurenine, and lipid metabolism, show 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.
AB - Purpose: 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. Experimental design: 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 tuberculosis (ATB: n = 22), non-tuberculosis (NTB: n = 18), and healthy subjects (n = 18). Serum small EVs proteome analysis is carried out using isobaric tag for relative and absolute quantification (iTRAQ) experiments and an independent sample (n = 36) is used for validation. Results: A set of 132 and 68 proteins are identified in iTRAQ-I (ATB/Healthy) and iTRAQ-II (ATB/NTB) experiments, respectively. Four proteins (KYAT3, SERPINA1, HP, and APOC3) show deregulation (log2-fold change >àñ0.48, pà<à0.05) in ATB with respect to healthy controls and Western blot data corroborated mass spectrometry findings. Conclusions and clinical relevance: These important proteins, involved in neutrophil degranulation, plasma heme scavenging, kynurenine, and lipid metabolism, show 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.
KW - extracellular vesicles
KW - immune response
KW - proteomics
KW - tuberculosis
UR - https://hdl.handle.net/1959.7/uws:54840
U2 - 10.1002/prca.201900062
DO - 10.1002/prca.201900062
M3 - Article
SN - 1862-8346
VL - 14
JO - Proteomics: Clinical Applications
JF - Proteomics: Clinical Applications
IS - 1
M1 - 1900062
ER -
