ABSTRACT
The tuberculin skin test [TST] and interferon-gamma release assays [IGRA], namely, the QuantiFERON-TB Gold test [QFT], remain the standard immuno-logical diagnostic tools for latent tuberculosis [TB] infection [LTBI]. However, the sub-optimal detection rates of both of these tests are major impediments in recognizing the population at risk. This study was aimed at evaluating additional cytokines besides interferon-gamma [IFN-gamma] as biomarkers for improving LTBI diagnosis in the tribal population of Melghat, India. Seventy-four close TB contacts were stratified by QFT and TST results into: [i] QFT+/TST+ [n = 26], [ii] QFT+/TST- [n = 12], [iii] QFT-/TST- [n = 35] and [iv] QFT-/TST+ [n = 1] groups. A panel of cytokines [IL-6, IL-10, TNF-alpha and IL-2R] was then evaluated in antigen-stimulated QFT cell-free culture supernatants using IMMULITE-1000, an automated immunoassay analyzer. Cytokine estimation showed significantly higher levels of IL-6 in the QFT+/TST+ group, while significantly higher levels of IL-10 were found in the QFT-/TST- group. Correlation analysis identified a positive correlation between IL-6 and the QFT response [r = 0.6723, P< 0.0001], while a negative correlation was seen between QFT and IL-10 expression [r=-0.3271, P = 0.0044]. Similarly, IL-6 was positively correlated with TST levels [r = 0.6631, P< 0.0001], and conversely, a negative correlation was found between TST and IL-10 expression [r=-0.5698, P<0.0001]. The positive and negative predictive values of IL-6 were found to be 92.59 and 93.33%, respectively, and the positive and negative predictive values of IL-10 were 96.55 and 91.18%, respectively. No significant impact of the demographic characteristics on cytokine positivity was observed. Our preliminary results suggest that the evaluation of additional cytokines in QFT cell-free culture supernatants may be valuable for the identification of LTBI. Combining IL-6 and IL-10 with QFT and/or TST could markedly improve the detection accuracy of LTBI. Our observations require investigation in larger well-characterized cohorts along with follow-up studies to further confirm the study outcome