Abstract
We aimed to determine whether shotgun proteomic approaches could be used to identify tuberculosis (TB)-specific biomarkers in the urine of well-characterised patients with active TB versus no TB.
Patients with suspected TB (n=63) were classified as: definite TB (Mycobacterium tuberculosis positive culture, n=21); presumed latent-TB infection (LTBI) (M. tuberculosis negative culture, no radiological features of active TB, a positive QuantiFERON-TB Gold In-Tube (QFT-IT) test and a positive T-SPOT.TB test, n=24); and presumed non-TB/non-LTBI (M. tuberculosis negative culture, no radiological features of active TB, a negative QFT-IT test and a negative T-SPOT.TB test, n=18). Urine proteins, in the range of 3–50 kDa, were collected, separated by a one-dimensional SDS-PAGE gel and digested using trypsin, after which high-performance liquid chromatography-tandem mass spectrometry was used to identify the urinary proteome.
10 mycobacterial proteins were observed exclusively in the urine of definite TB patients, while six mycobacterial proteins were found exclusively in the urine of presumed LTBI patients. In addition, a gene ontology enrichment analysis identified a panel of 20 human proteins that were significant discriminators (p<0.05) for TB disease compared to no TB disease. Furthermore, seven common human proteins were differentially over- or under-expressed in the TB versus the non-TB group.
These biomarkers hold promise for the development of new point-of-care diagnostics for TB.
Abstract
The application of proteomics for the identification of novel urinary tuberculosis biomarkers http://ow.ly/tN0Rm
Footnotes
This article has supplementary material available from www.erj.ersjournals.com
Support statement: J. Blackburn thanks the Department of Science and Technology and the National Research Foundation for a South African Research Chair Initiative grant. B.L. Young thanks the Carnegie Corporation for a postdoctoral research fellowship. The work was funded by the National Research Foundation (grant no. 64760) and the TB-NEAT grant from the European and Developing Countries Clinical Trials Partnership (grant number 09.32040.009).
Conflict of interest: Disclosures can be found alongside the online version of this article at www.erj.ersjournals.com
- Received October 7, 2013.
- Accepted February 13, 2014.
- ©ERS 2014