Granzyme B as a diagnostic marker of tuberculosis in patients with and without HIV coinfection

Immunodiagnostic tests for tuberculosis (TB) are based on the estimation of interferon γ (IFN-γ) or IFN-γ-secreting CD4+ T cells following ex vivo stimulation with ESAT6 and CFP-10. Sensitivity of these tests is likely to be compromised in CD4+ T-cell-depleted situations, like HIV-TB coinfection. CD4+ and CD8+ T cells, isolated from 3 groups, viz., HIV-negative patients with active TB, HIV-TB coinfected patients, and healthy household contacts (HHCs) were cocultivated with autologous dendritic cells, and the cytokine response to rESAT6 stimulation was compared between groups in supernatants. While CD4+ T-cell stimulation yielded significantly elevated levels of IFN-γ and interleukin 4 in HIV-negative TB patients, compared to HHCs, the levels of both these cytokines were nondiscriminatory between HIV-positive TB patients and HHCs. However, CD8+ T-cell stimulation yielded significantly elevated granzyme B titers in both groups of patients, irrespective of HIV coinfection status. Hence, contrary to IFN-γ, granzyme B might be a useful diagnostic marker for Mycobacterium tuberculosis infection particularly in HIV coinfected patients.