Host markers in QuantiFERON supernatants differentiate active TB from latent TB infection: Preliminary report
IGRAs do not discriminate between active TB and LTBI and so have limited value in high-burden TB settings. There is a need to develop rapid diagnostic tests for active TB. If especially T-cell-based assays are to be developed for this purpose, then the way forward would be to identify alternative antigens other than ESAT-6/CFP-10/TB7.7, which are used in the currently available IGRAs, or alternative markers other than IFN-γ. The development of the Luminex xMAP technology has made it possible to measure multiple (up to 100) biomarkers in small (25-50 μl) amounts of sample. In this study, it was hypothesized that stimulation of whole blood with M. tuberculosis-specific antigens would result in the production of multiple biomarkers, some of which would be unique to either LTBI or active TB disease. The researchers looked at the ability of 29 analytes to discriminate between QFT-positive supernatants as active TB or LTBI and to differentiate between TB cases and contacts regardless of QFT results. They found that unstimulated levels of EGF (EGFNil) marker showed a sensitivity of 91.3% and a specificity of 79.4% in discriminating between TB patients and contacts regardless of QFT results. The EGFAg-Nil marker showed a sensitivity of 91.2% and a specificity of 82.6%. The sCD40L Nil marker showed a sensitivity of 86.9% and a specificity of 79.4%. They found that combinations of analytes are more promising than individual analytes. The top individual analytes were EGFNil, EGFAg, EGFAg-Nil, sCD40LNil, and MIP-1βAg-Nil. It was concluded that multiple biomarkers measured in QFT supernatants show the potential to discriminate accurately between active TB and the absence of active disease. So these researchers propose a two-step test system: 1) IFN-γ or IP-10 detection to diagnose M. tuberculosis infection, and 2) measurement of the levels of EGF or MIP-1β to differentiate positive IFN-γ or IP-10 results as active TB or LTBI. This approach holds promise and should be pursued for development as a rapid test for active TB. © 2010 The Union.