Modulation of interferon-gamma response to QuantiFERON-TB-plus detected by enzyme-linked immunosorbent assay in patients with active and latent tuberculosis infection

Abstract

Objective/Background: Interferon (IFN)-γ-release assays (IGRAs) are designed for the diagnosis of tuberculosis (TB) infection. The new IGRA called QuantiFERON-TB Plus (QFT-Plus) is based on enzyme-linked immunosorbent assay (ELISA) detection of IFN-γ following Myobacterium tuberculosis-antigen stimulation with TB1 and TB2 antigens. TB1 elicits a cell-mediated immune response by CD4 T cells and TB2 elicits a response from both CD4 and CD8 T cells. Here, we characterized variations IFN-γ release detected by ELISA to QFT-IT and QFT-Plus in patients with active TB and latent TB infection (LTBI) at baseline and during or after specific treatment (follow-up). Methods: We studied seven patients with active TB and 10 patients with LTBI at baseline and during treatment either for active disease or preventive therapy. IFN-γ release detected by ELISA to QFT-IT and QFT-Plus was concomitantly evaluated over time. Statistical analysis was performed using a nonparametrical test for a paired dataset (Wilcoxon test). Results: All participants responded to the mitogen, with all active-TB patients responding to QFT-IT or QFT-Plus at baseline. The responses did not change over time either qualitatively (number of responders) or quantitatively (IFN-γ release evaluated as IU/mL). Among the LTBI group, although all participants responded to both QFT-IT and QFT-Plus and the responses did not change over time, the quantitative responses to QFT-Plus showed a different trend. Specifically, response to TB2 was significantly lower at follow-up as compared with that observed at baseline (p = 0.004), whereas the response to TB1 was not significantly different (p = 0.16). Conclusion: To our knowledge, this is the first report characterizing IFN-γ responses to QFT-Plus antigens in participants with active TB and LTBI over time. The data need to be confirmed in larger settings; however, we showed that monitoring IFN-γ release in response to TB2 can be used to evaluate preventive therapy immune changes. This can be useful also as a tool for public health control strategies in settings where preventive treatment is recommended.

Keywords

• Tuberculosis
• Quantiferon-Plus
• Latency
• Infection
• Diagnosis