Interpretation of Mycobacterium tuberculosis antigen-specific IFN-gamma release assays (T-SPOT.TB) and factors that may modulate test results

J Infect. 2007 Aug;55(2):169-73. doi: 10.1016/j.jinf.2007.02.005. Epub 2007 Apr 19.


Background: Data about T cell antigen-specific (ESAT-6 and CFP-10) IFN-gamma release assays (IGRAs) during and after completion of anti-tuberculous (TB) treatment are limited and highly discordant. Thus, the utility of IGRAs as a surrogate marker of mycobacterial burden remain unclear.

Methods: To investigate factors that modulate IGRA responses during anti-TB treatment we used a standardised assay (T-SPOT.TB) in 33 patients with culture positive tuberculosis.

Results: Significantly more patients in the early (< or = 4 months of anti-TB treatment) rather than the late phase (> 4 months or completed anti-TB treatment) had positive IGRA responses [10/12 (83%) vs 4/21 (19%); p < or = 0.01]. Thus, 17/21 (81%) in the late phase or who had completed treatment (mean duration of treatment = 8.7 months) were IGRA negative, despite having robust antigen-specific recall proliferative responses. In these 17 patients prolonged incubation (5 days vs overnight), use of different antigen preparations (protein vs peptide) and addition of endotoxin, failed to elicit positive responses.

Conclusions: In treated TB patients the discordant IGRA data remain unexplained by variation in laboratory protocols and are more likely due to host or environmental factors. In a low burden setting IGRAs may be a promising surrogate marker of mycobacterial disease burden.

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / isolation & purification
  • Bacterial Proteins / immunology*
  • Female
  • Humans
  • Interferon-gamma / biosynthesis*
  • Male
  • South Africa
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / metabolism


  • Antigens, Bacterial
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Mycobacterium tuberculosis antigens
  • Interferon-gamma