In vitro QuantiFERON-TB gold antigen specific interleukin-1beta to diagnose TB among HIV-positive subjects

The recently introduced IFN-γ release assay (IGRA) has been reported to improve the diagnosis of TB. However, IGRA has suboptimal sensitivity to diagnose TB among HIV co-infected subjects. Apart from IFN-γ, the pro inflammatory cytokines such as Interleukin-1beta (IL-1β), Tumor necrosis factor-alpha (TNF-α), IL-2, IL-6, IL-8 and IL-12 are also play a major role in mycobacterial infections. This study aimed to analyze these cytokines for detecting active TB among HIV sero positive subjects.

We had prospectively enrolled 53 HIV positive subjects and 55 HIV-TB co-infected patients from India. IGRA was performed by using QuantiFERON TB-Gold In tube (QFT-GIT) method. TB antigen specific IL-1β, TNF-α, IL-2, IL-6, IL-8 and IL-12 levels were evaluated by ELISA in plasma harvested from QFT-GIT tubes.

The TB antigen specific IL-1β levels were significantly elevated in HIV-TB co-infected patients compared to HIV positive subjects (p = 0.0004). The specificity of both IL-1β (50.94%) and QFT-GIT (52.83%) remained similar in HIV positive subjects (p = 0.24). However, IL-1β had shown higher sensitivity (72.73%) than QFT-GIT (54.55%) to diagnose TB among HIV co-infected patients. Moreover, in culture test positive HIV-TB patients, antigen specific IL-1β exhibited sensitivity of 84.21%; whereas QFT-GIT exhibited only 57.89% sensitivity. Unlike IFN-γ (the read out marker of QFT-GIT), antigen specific IL-1β levels were not influenced by low CD4 counts. The other cytokine levels were not significantly differ between the 2 groups.From this study we concluded that TB antigen specific IL-1β may be an additional biomarker for active TB diagnosis among HIV positive subjects.