Association between tuberculosis recurrence and interferon-γ response during treatment

J Infect. 2014 Dec;69(6):616-26. doi: 10.1016/j.jinf.2014.06.007. Epub 2014 Jun 21.


Objectives: We investigated the relationship between tuberculosis recurrence and Mycobacterium tuberculosis antigen-stimulated interferon-gamma (IFN-γ) responses during treatment.

Methods: Plasma IFN-γ levels in active pulmonary tuberculosis patients (n = 407) were analyzed using QuantiFERON-TB Gold In-Tube™ (QFT-IT) at 0, 2, and 7 months of the 8-month treatment received from 2007 to 2009 and the patients were followed up for another 16 months after treatment. Risk factors for recurrence were assessed using the log-rank test and Cox proportional hazard models. Random coefficient models were used to compare longitudinal patterns of IFN-γ levels between groups.

Results: QFT-IT showed positive results in 95.6%, 86.2%, and 83.5% at 0, 2, and 7 months, respectively. The antigen-stimulated IFN-γ responses varied significantly during the treatment course (P < 0.0001). Unexpectedly, positive-to-negative conversion of QFT-IT results between 0 and 2 months was significantly associated with earlier recurrence (adjusted hazard ratio, 5.57; 95% confidence interval, 2.28-13.57). Time-dependent changes in IFN-γ levels were significantly different between the recurrence and nonrecurrence groups (P < 0.0001).

Conclusions: Although the IGRA response varies individually, early response during the treatment course may provide an insight into host immune responses underlying tuberculosis recurrence.

Keywords: Cellular response; Interferon-γ release assay; Recurrence; Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / blood
  • Antigens, Bacterial / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Interferon-gamma / blood*
  • Interferon-gamma / immunology*
  • Interferon-gamma Release Tests / methods*
  • Interleukin 1 Receptor Antagonist Protein / blood
  • Interleukin-2 / blood
  • Logistic Models
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • Recurrence
  • Risk Factors
  • Tuberculosis, Pulmonary / immunology*


  • Antigens, Bacterial
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-2
  • Interferon-gamma