Modulation of QuantiFERON-TB-Gold Plus response in patients with active tuberculosis and latent infection during treatment

Abstract

Introduction: Interferon (IFN)γ release assays (IGRA) are designed for diagnosing tuberculosis (TB) infection. The new IGRA called QuantiFERON-TB- Gold Plus (QFT-Plus), is based on the detection of IFNγ after stimulation with M. tuberculosis (Mtb) TB1 and TB2 peptides. TB1 peptides stimulates the CD4 T-cells and TB2 both CD4 and CD8. Aims: to monitor the QFT-Plus response in active TB patients and subjects with latent TB infection (LTBI) at baseline, during and after treatment. Methods: We enrolled 17 active TB patients and 18 LTBI subjects. We performed the QFT-Plus and QFT- GOLD in tube (GIT) over the time. Wilcoxon and Friedman tests were applied. Results: QFT-Plus and QFT-GIT showed same sensitivity in LTBI subjects (100%), whereas in active TB the QFT-Plus displayed higher sensitivity compare to QFT-GIT (88% vs 76%). All patients responded to mitogen. LTBI subjects after prophylaxis showed a significantly decrease of IFNγ level in response to TB2, compared to the baseline (p=0.01). In 14 LTBI subjects followed for three time points, we found a significant decrease of the IFNγ in response to TB2 compared to the baseline, after 2 months (p=0.02) and at the end of therapy (p=0.0007). No significant differences were found in response to QFT-GIT antigens. Active TB patients did not show differences of IFNγ production overtime in response to either test. Conclusions: We demonstrated similar accuracy of QFT-Plus and QFT-GIT for TB detection. In LTBI the preventive therapy decreases the IFNγ response to TB2, probably due to the diminished CD8 response. The study of CD8 response using the TB2 peptides may be useful to monitor the effect of the preventive treatment.