Open Access

ARTICLE

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

Johannes Nemeth^1,3, Heide-Maria Winkler¹, Franz Karlhofer², Nicole Selenko-Gebauer², Wolfgang Graninger¹, Stefan Winkler¹

1 Department of Internal Medicine I, Division of Infectious Diseases, Medical University of Vienna, Austria
2 Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Austria
3 Department of Medicine, University Hospital of Basel, Basel, Switzerland

* Corresponding Author: S. Winkler,

European Cytokine Network 2010, 21(1), 34-39. https://doi.org/10.1684/ecn.2009.0182

Accepted 07 December 2009;

Abstract

Patients treated with tumor necrosis factor (TNF)-α-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-α-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 imple-mentation of anti-TNF-α therapy. Mycobacterium tuberculosis (MTB)-specific cytokine production, including interferon (IFN)-γ, TNF-α, 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 deriva-tive (PPD) and early secretion antigenic target (ESAT)-6. Simultaneously, a TST was administered and 11 were TST-positive. Generally, MTB-specific IFN-γ produced by CD4⁺ T cells correlated well with TST results. CD4+ T cells co-producing specific IFN-γ and TNF-α after ESAT-6 stimulation showed the highest overall agreement with the TST (Kappa [κ] = 0.87). Each single cytokine displayed individual patterns, the expression of IFN-γ, however, showed the highest concordance with the TST (κ = 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.

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