T cells co-producing Mycobacterium tuberculosis-specific type 1 cytokines for the diagnosis of latent tuberculosis.

Patients treated with tumor necrosis factor (TNF)-alpha-antagonizing medication are at increased risk of developing active tuberculosis (TB), brought about mainly by reactivation of latent infection. Thus, screening for latent TB infection (LTBI) prior to administration of anti-TNF-alpha-therapy is required. For a long time, the tuberculin skin test (TST) was the only means of diagnosing LTBI, however, interferon-gamma-release assays (IGRAs), are promising new tools. Fifty two patients with dermatological disorders were included prior to implementation of anti-TNF-alpha therapy. Mycobacterium tuberculosis (MTB)-specific cytokine production, including interferon (IFN)-gamma, TNF-alpha, interleukin (IL)-2 and IL-10, was measured in CD4+ and CD8+ T cells by cytokine flow cytometry following stimulation of peripheral blood mononuclear cells (PBMC) with purified protein derivative (PPD) and early secretion antigenic target (ESAT)-6. Simultaneously, a TST was administered and 11 were TST-positive. Generally, MTB-specific IFN-gamma produced by CD4+ T cells correlated well with TST results. CD4+ T cells co-producing specific IFN-gamma and TNF-alpha after ESAT-6 stimulation showed the highest overall agreement with the TST (Kappa [kappa] = 0.87). Each single cytokine displayed individual patterns, the expression of IFN-gamma, however, showed the highest concordance with the TST (kappa = 0.82). This suggests that the enumeration of MTB-specific CD4+ T cells might introduce greater specificity for the diagnosis of latent TB, compared to the TST.