Sensitivity of a whole-blood interferon-gamma assay among patients with pulmonary tuberculosis and variations in T-cell responses during anti-tuberculosis treatment

Interferon-gamma (IFN-gamma) assays are new tests for tuberculosis (TB) infection, and T-cell responses may be correlated with antigen burden. However, it is unclear if IFN-gamma assays can be used to monitor response to TB treatment. We measured T-cell responses to TB specific antigens in 60 Indian patients with microbiologically confirmed active pulmonary tuberculosis, before, during, and after TB treatment. Most patients were hospitalized and had moderate to advanced disease. IFN-gamma responses were measured using the commercial whole-blood Quanti-FERON-TB Gold In Tube (QFT-G) assay at three time-points: at diagnosis (N = 60), after 2 months of intensive treatment (N = 47), and at 6 months (treatment completion) (N = 39). At baseline, 44 of 60 (73%) patients were positive by QFT-G. At the second time-point, 38 of 47 (81%) patients were positive. At treatment completion, 31 of 39 (79%) patients were positive. Changes in IFN-gamma responses over time were highly inconsistent - some individuals showed increases, while others showed decreases or no changes. Although the average IFN-gamma levels decreased slightly during treatment (not significant), the QFT-G sensitivity remained mostly unchanged during therapy. Our data suggest that the QFT-G assay has modest sensitivity in patients with moderate to advanced pulmonary disease, but our results do not show a clear correlation between antigen burden and T-cell responses. Further research is needed to understand the kinetics of Tcell responses during TB treatment.