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

BACKGROUND: 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-1ß), 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. MATERIALS AND METHODS: 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-1ß, TNF-α, IL-2, IL-6, IL-8 and IL-12 levels were evaluated by ELISA in plasma harvested from QFT-GIT tubes. RESULTS AND CONCLUSION: The TB antigen specific IL-1ß levels were significantly elevated in HIV-TB co-infected patients compared to HIV positive subjects (p = 0.0004). The specificity of both IL-1ß (50.94%) and QFT-GIT (52.83%) remained similar in HIV positive subjects (p = 0.24). However, IL-1ß 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-1ß 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-1ß 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-1ß may be an additional biomarker for active TB diagnosis among HIV positive subjects.

IFN-gamma, but not IP-10, MCP-2 or IL-2 response to RD1 selected peptides associates to active tuberculosis.

OBJECTIVES: To evaluate whether in vitro response to Mycobacterium tuberculosis RD1 peptides selected by computational analysis, measured by IFN-gamma, IP-10, MCP-2 or IL-2 production, is associated with active tuberculosis (TB) in a country with a high incidence of TB. METHODS: 129 individuals were prospectively enrolled, 41 with active-pulmonary TB and 88 without (household contacts and community controls). A whole blood assay based on RD1 selected peptides was performed. Soluble factors were evaluated by ELISA in plasma harvested at day1-post-culture. Enrolled individuals were also tested by QuantiFERON TB-Gold In tube (QFT-IT) and tuberculin skin tests (TST). RESULTS: IFN-gamma response to RD1 selected peptides was significantly higher in active TB patients than in household contacts and community controls. IP-10 and MCP-2 response did not differ between active TB patients and household contacts, although it was higher in these groups compared to community controls; conversely IL-2 response did not differ among the three groups. When IFN-gamma response to RD1 selected peptides was scored based on receiver-operator-characteristic analysis, active TB was predicted with 68% sensitivity and 86% specificity. QFT-IT and TST showed a sensitivity for active TB of 90% and 68% and a specificity of 58% and 59%, respectively. CONCLUSIONS: IFN-gamma (but not IP-10, MCP-2 and IL-2) response to RD1 selected peptides is associated with active TB with a higher specificity than QFT-IT and TST.