QuantiFERON-TB Gold Plus Assay in Patients With Latent vs. Active Tuberculosis in a Low Incidence Setting: Level of IFN-gamma, CD4/CD8 Responses, and Release of IL-2, IP-10, and MIG

Objectives: We analyzed the results of the QuantiFERON Glod Plus assay (QFT) and cytokine patterns associated with active tuberculosis (ATB) among patients with positive QFT. Methods: A total of 195 patients are QFT-positive, among which 24 had an ATB and 171 had a latent tuberculosis infection (LTBI). Interferon-gamma (IFN-gamma) secretion was analyzed relative to interleukin-2 (IL-2), IFN-gamma inducible protein or CXCL-10 (IP-10), and monokine induced by IFN-gamma or CXCL-9 (MIG) secretion, and then compared between two sets of peptide antigens [tube 1 - cluster of differentiation 4 (CD4(+)) T cell stimulation; tube 2 - CD4(+)/CD8(+) T cell response]. Results: Higher IFN-gamma responses were measured in the ATB group (p = 0.0089). The results showed that there was a lower ratio of tube 1/tube 2 IFN-gamma concentrations in the ATB group (p = 0.0009), and a median [interquartile ranges (IQR)] difference between the two sets at -0.82 IU/ml (-1.67 to 0.18) vs. -0.07 IU/ml (-0.035 to 0.11, p < 0.0001) in the ATB group compared to the LTBI group, respectively. In addition, patients with low ratios of IL-2/IFN-gamma, IP-10/IFN-gamma, and MIG/IFN-gamma were much more likely to have ATB. Conclusion: High levels of IFN-gamma secretion, preferential IFN-gamma response in tube 2, and lower secretion of IL-2, IP-10, and MIG release relative to IFN-gamma secretion were more likely observed in subjects with ATB. These features of T cell response may be helpful in low prevalence settings to suspect ATB in patients tested positive for IFN-gamma release assays (IGRA).