LAUSR

Introduction: It would be important to identify subjects at risk to develop tuberculosis (TB) disease. RD1-based Interferon-γ Release Assays (IGRAs) cannot distinguish latent from active TB disease. Conversely, a positive response to HBHA-based IGRAs, among TB-infected subjects, correlates with Mtb containment and low risk of TB progression. Aims: to characterize HBHA-immune responses in HIV-infected and uninfected subjects with active TB or latent TB infection (LTBI). Methods: 49 subjects were prospectively enrolled, 22 HIV-uninfected (13 TB, 9 LTBI) and 27 HIV-infected (12 HIV-TB, 15 HIV-LTBI). Whole blood and PBMC were stimulated with HBHA and RD1 antigens. IFNγ release was evaluated by ELISA whereas cytokine profile (IFNγ, TNFα, IL2) and phenotype (CD45RA, CD27) by FACS. Results: Among LTBI individuals, HBHA stimulation induced IFNγ release in all the HIV-uninfected, while only 4/15 HIV-infected responded. Within the active TB, only 6/13 HIV-uninfected and 1/12 HIV-TB patients responded. Differently than what observed for RD1, the cytokine profile of HBHA-specific T cells evaluated by FACS showed that the CD4 T cells were mostly monofunctional. Conversely, CD8-specific T cells were mostly monofunctional for both HBHA and RD1 stimulations. The phenotype of HBHA-specific T cells showed a predominantly central memory (CM) and effector memory (EM) phenotype in CD4 T cells without differences among the groups. Differently, HBHA-specific CD8 T cells, showed mainly a CM and naive phenotype in LTBI group while TB, HIV-LTBI and HIV-TB groups were characterized by EM or TEMRA phenotypes. Conclusions: These results may help to better define immunological correlates of protection from TB disease.