Quantitative proteomics for identifying biomarkers for tuberculous meningitis

定量蛋白质组学用于鉴定结核性脑膜炎的生物标志物

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作者:Ghantasala S Sameer Kumar, Abhilash K Venugopal, Anita Mahadevan, Santosh Renuse, H C Harsha, Nandini A Sahasrabuddhe, Harsh Pawar, Rakesh Sharma, Praveen Kumar, Sudha Rajagopalan, Keith Waddell, Yarappa L Ramachandra, Parthasarathy Satishchandra, Raghothama Chaerkady, T S Keshava Prasad, K Shankar,

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.

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.

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