Comparison of interferon gamma-inducible protein-10 and interferon gamma-based QuantiFERON TB Gold assays with tuberculin skin test in HIV-infected subjects

Abstract

We aimed to compare the positivity of the QuantiFERON TB gold in-tube (QFT-IT antigens) specific interferon gamma (IFN-γ/QFT-IT) and IFN-γ-inducible protein-10 (IP-10/QFT-IT) assays with tuberculin skin test (TST) among human immunodeficiency virus (HIV)-infected individuals in a TB endemic setting. A total of 180 HIV-infected subjects, with no evidence of active TB, were recruited. IFN-γ and IP-10 levels specific to QFT-IT antigens were measured in plasma from QFT-IT tubes. The overall positivity of TST at the 5-mm cut-off point (19%) was significantly lower when compared to IFN-γ/QFT-IT (38%) and IP-10/QFT-IT (45%) assays. The positivity of IP-10/QFT-IT was significantly higher than that of IFN-γ/QFT-IT (P = 0.038). Indeterminate results for IFN-γ/QFT-IT and IP-10/QFT-IT were more frequent in subjects with CD4 count <100 cells/μL than in those with >100 cells/μL. IFN-γ/QFT-IT (9%) yielded significantly higher number of indeterminate results than IP-10/QFT-IT (5%). The frequency of these responses is higher than the proportion of individuals with positive TST results. However, 6 IFN-γ/QFT-IT- or IP-10/QFT-IT-negative subjects were positive for TST at the 5-mm cut-off point. Prospective and prognostic studies are required to clarify the significance of these data.

Figure 1. The levels of IFN-γ (a) and IP-10 (b) secretion in QFT-IT NIL, QFT-IT TB antigen stimulated and QFT-IT mitogen stimulated samples

The levels of IFN-γ and IP-10 were significantly higher in QFT-IT TB antigens stimulated, as well as QFT-IT mitogen stimulated samples when compared to QFT-IT NIL samples. Box and Whisker plots show range, inter-quartile range and median. The difference between the groups was calculated by Kruskal-Wallis test. *significant difference p<0.001 compared to unstimulated sample, # significant difference p<0.001 compared to QFT-IT TB specific antigens stimulated sample. QFT-IT – QuantiFERON-TB Gold in-tube, TB- Tuberculosis

Figure 1. The levels of IFN-γ (a) and IP-10 (b) secretion in QFT-IT NIL, QFT-IT TB antigen stimulated and QFT-IT mitogen stimulated samples

The levels of IFN-γ and IP-10 were significantly higher in QFT-IT TB antigens stimulated, as well as QFT-IT mitogen stimulated samples when compared to QFT-IT NIL samples. Box and Whisker plots show range, inter-quartile range and median. The difference between the groups was calculated by Kruskal-Wallis test. *significant difference p<0.001 compared to unstimulated sample, # significant difference p<0.001 compared to QFT-IT TB specific antigens stimulated sample. QFT-IT – QuantiFERON-TB Gold in-tube, TB- Tuberculosis

Figure 2. The influence of CD4 count on IFN-γ/QFT-IT (a), IP-10/QFT-IT (b) assays and TST (c) outcomes

The decline of CD4 count was associated with IFN-γ/QFT-IT or IP-10/QFT-IT indeterminate only but not with IFN-γ/QFT-IT or IP-10/QFT-IT negative. The CD4 count was significantly low in TST negatives than TST positives. Box and Whisker plots show range, inter-quartile range and median. QFT-IT–Quantiferon TB Gold in-tube, IP-10 – Interferon gamma inducible protein-10, TST – Tuberculin skin test, *significant difference p<0.05 by Kruskal-Wallis test.

Figure 2. The influence of CD4 count on IFN-γ/QFT-IT (a), IP-10/QFT-IT (b) assays and TST (c) outcomes

The decline of CD4 count was associated with IFN-γ/QFT-IT or IP-10/QFT-IT indeterminate only but not with IFN-γ/QFT-IT or IP-10/QFT-IT negative. The CD4 count was significantly low in TST negatives than TST positives. Box and Whisker plots show range, inter-quartile range and median. QFT-IT–Quantiferon TB Gold in-tube, IP-10 – Interferon gamma inducible protein-10, TST – Tuberculin skin test, *significant difference p<0.05 by Kruskal-Wallis test.

Figure 2. The influence of CD4 count on IFN-γ/QFT-IT (a), IP-10/QFT-IT (b) assays and TST (c) outcomes

The decline of CD4 count was associated with IFN-γ/QFT-IT or IP-10/QFT-IT indeterminate only but not with IFN-γ/QFT-IT or IP-10/QFT-IT negative. The CD4 count was significantly low in TST negatives than TST positives. Box and Whisker plots show range, inter-quartile range and median. QFT-IT–Quantiferon TB Gold in-tube, IP-10 – Interferon gamma inducible protein-10, TST – Tuberculin skin test, *significant difference p<0.05 by Kruskal-Wallis test.