Elevated host lipid metabolism revealed by iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid of tuberculous meningitis patients.
OBJECTIVE
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.
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Jun
J
Mu
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Yongtao
Y
Yang
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Jin
J
Chen
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Ke
K
Cheng
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Qi
Q
Li
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Yongdong
Y
Wei
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Dan
D
Zhu
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Weihua
W
Shao
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China.
Peng
P
Zheng
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China. Electronic address: xiepeng@cqmu.edu.cn.
Peng
P
Xie
D000328:Adult; D001055:Apolipoproteins B / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008587:Meningitis, Viral / Q000134:cerebrospinal fluid / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000378:metabolism / Q000472:pathogenicity; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid* / Q000378:metabolism* / Q000382:microbiology; D055815:Young Adult
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D015415:Biomarkers
ApoB; Cerebrospinal fluid; Proteomic; Tuberculous meningitis; iTRAQ