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Background  An IFN-γ response to  M. tuberculosis -specific antigens is an effective biomarker for  M. tuberculosis  infection but it cannot discriminate between latent TB infection and active TB disease. Combining a number of cytokine/chemokine responses to  M. tuberculosis  antigens may enable differentiation of latent TB from active disease.    Methods  Asymptomatic recently-exposed individuals (spouses of TB patients) were recruited and tuberculin skin tested, bled and followed-up for two years. Culture supernatants, from a six-day culture of diluted whole blood samples stimulated with  M. tuberculosis -derived PPD or ESAT-6, were measured for IFN-γ, IL-10, IL-13, IL-17, TNF-α and CXCL10 using cytokine ELISAs. In addition, 15 patients with sputum smear-positive pulmonary TB were recruited and tested.    Results  Spouses with positive IFN-γ responses to  M. tuberculosis  ESAT-6 (>62.5 pg/mL) and TB patients showed high production of IL-17, CXCL10 and TNF-α. Higher production of IL-10 and IL-17 in response to ESAT-6 was observed in the spouses compared with TB patients while the ratios of IFN-γ/IL-10 and IFN-γ/IL-17 in response to  M. tuberculosis -derived PPD were significantly higher in TB patients compared with the spouses. Tuberculin skin test results did not correlate with cytokine responses.    Conclusions  CXCL10 and TNF-α may be used as adjunct markers alongside an IFN-γ release assay to diagnose  M. tuberculosis  infection, and IL-17 and IL-10 production may differentiate individuals with LTBI from active TB.

Combination of Cytokine Responses Indicative of Latent TB and Active TB in Malawian Adults