title: iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis.
abstract: Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. As TBM may result in permanent sequelae and death, rapid, accurate diagnostic tests using novel biomarkers are required for the early diagnosis and treatment of TBM. A quantitative proteomic study was therefore performed to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n=12) and healthy controls (n=12). CSF samples were labelled with iTRAQ™ and analyzed by LC-MS/MS. Gene ontology and Pathway analysis were conducted using DAVID bioinformatics resources. Neural epidermal growth factor-like like 2 (NELL2) with the largest fold-change value was selected for validation by western blotting. Proteomic phenotyping revealed over-representation in two inflammation-associated processes, complement and coagulation cascades as well as cell adhesion molecules. Western blotting showed a significant decrease in NELL2 levels in TBM subjects compared to healthy controls. The AUC analysis revealed NELL2 was able to distinguish TBM subjects from healthy controls with 83.3% sensitivity and 75% specificity. In conclusion, the results showed that CSF NELL2 is a potential diagnostic biomarker for TBM. Further evaluation of these findings in larger studies including anti-tuberculosis medicated and unmedicated patient cohorts with other intracranial infectious diseases is required for clinical translation.
authors.affiliation: Department of Neurology, The First Afﬁliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, The First Afﬁliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mu
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Chen
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Jiaju
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Neurology, The First Afﬁliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Youdong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Neurology, The First Afﬁliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Neurology, The First Afﬁliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qin
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Neurology, The First Afﬁliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000328:Adult; D015415:Biomarkers; D019295:Computational Biology / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid*; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C104145:NELL2 protein, human; D009419:Nerve Tissue Proteins