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Author Mu, Jun ♦ Yang, Yongtao ♦ Chen, Jin ♦ Cheng, Ke ♦ Li, Qi ♦ Wei, Yongdong ♦ Zhu, Dan ♦ Shao, Weihua ♦ Zheng, Peng ♦ Xie, Peng
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ CEREBROSPINAL FLUID ♦ CESIUM FLUORIDES ♦ ENZYME IMMUNOASSAY ♦ GENES ♦ LIQUID COLUMN CHROMATOGRAPHY ♦ MASS SPECTROSCOPY ♦ METABOLISM ♦ MYCOBACTERIUM TUBERCULOSIS ♦ NERVOUS SYSTEM ♦ PATHOGENESIS ♦ PATHOGENS ♦ PATIENTS ♦ PHENOTYPE ♦ PROTEINS ♦ SENSITIVITY ♦ SPECIFICITY ♦ TUBERCULOSIS
Abstract Purpose: Tuberculous meningitis (TBM) remains to be one of the most deadly infectious diseases. The pathogen interacts with the host immune system, the process of which is largely unknown. Various cellular processes of Mycobacterium tuberculosis (MTB) centers around lipid metabolism. To determine the lipid metabolism related proteins, a quantitative proteomic study was performed here to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n = 12) and healthy controls (n = 12). Methods: CSF samples were desalted, concentrated, labelled with isobaric tags for relative and absolute quantitation (iTRAQ™), and analyzed by multi-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene ontology and proteomic phenotyping analysis of the differential proteins were conducted using Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. ApoE and ApoB were selected for validation by ELISA. Results: Proteomic phenotyping of the 4 differential proteins was invloved in the lipid metabolism. ELISA showed significantly increased ApoB levels in TBM subjects compared to healthy controls. Area under the receiver operating characteristic curve analysis demonstrated ApoB levels could distinguish TBM subjects from healthy controls and viral meningitis subjects with 89.3% sensitivity and 92% specificity. Conclusions: CSF lipid metabolism disregulation, especially elevated expression of ApoB, gives insights into the pathogenesis of TBM. Further evaluation of these findings in larger studies including anti-tuberculosis medicated and unmedicated patient cohorts with other center nervous system infectious diseases is required for successful clinical translation. - Highlights: • The first proteomic study on the cerebrospinal fluid of tuberculous meningitis patients using iTRAQ. • Identify 4 differential proteins invloved in the lipid metabolism. • Elevated expression of ApoB gives insights into the pathogenesis of TBM.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-10-30
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 466
Issue Number 4


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