title: Quantitative proteomics for identifying biomarkers for tuberculous meningitis.
abstract: BACKGROUND
  Tuberculous meningitis is a frequent extrapulmonary disease caused by Mycobacterium tuberculosis and is associated with high mortality rates and severe neurological sequelae. In an earlier study employing DNA microarrays, we had identified genes that were differentially expressed at the transcript level in human brain tissue from cases of tuberculous meningitis. In the current study, we used a quantitative proteomics approach to discover protein biomarkers for tuberculous meningitis.
  
  
  METHODS
  To compare brain tissues from confirmed cased of tuberculous meningitis with uninfected brain tissue, we carried out quantitative protein expression profiling using iTRAQ labeling and LC-MS/MS analysis of SCX fractionated peptides on Agilent's accurate mass QTOF mass spectrometer.
  
  
  CONCLUSIONS
  Through this approach, we identified both known and novel differentially regulated molecules. Those described previously included signal-regulatory protein alpha (SIRPA) and protein disulfide isomerase family A, member 6 (PDIA6), which have been shown to be overexpressed at the mRNA level in tuberculous meningitis. The novel overexpressed proteins identified in our study included amphiphysin (AMPH) and neurofascin (NFASC) while ferritin light chain (FTL) was found to be downregulated in TBM. We validated amphiphysin, neurofascin and ferritin light chain using immunohistochemistry which confirmed their differential expression in tuberculous meningitis. Overall, our data provides insights into the host response in tuberculous meningitis at the molecular level in addition to providing candidate diagnostic biomarkers for tuberculous meningitis.
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India. shankarsk2004@gmail.com.
authors.forename: Ghantasala S Sameer
authors.initials: GS
authors.lastname: Kumar
authors.forename: Abhilash K
authors.initials: AK
authors.lastname: Venugopal
authors.forename: Anita
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authors.lastname: Mahadevan
authors.forename: Santosh
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authors.lastname: Renuse
authors.forename: H C
authors.initials: HC
authors.lastname: Harsha
authors.forename: Nandini A
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authors.lastname: Sahasrabuddhe
authors.forename: Harsh
authors.initials: H
authors.lastname: Pawar
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Praveen
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authors.lastname: Kumar
authors.forename: Sudha
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Keith
authors.initials: K
authors.lastname: Waddell
authors.forename: Yarappa L
authors.initials: YL
authors.lastname: Ramachandra
authors.forename: Parthasarathy
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authors.lastname: Satishchandra
authors.forename: Raghothama
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authors.lastname: Chaerkady
authors.forename: T S Keshava
authors.initials: TS
authors.lastname: Prasad
authors.forename: K
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authors.lastname: Shankar
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey