IP-10 response to RD1 antigens might be a useful biomarker for monitoring tuberculosis therapy

BMC Infect Dis. 2011 May 19:11:135. doi: 10.1186/1471-2334-11-135.

Abstract

Background: There is an urgent need of prognosis markers for tuberculosis (TB) to improve treatment strategies. The results of several studies show that the Interferon (IFN)-γ-specific response to the TB antigens of the QuantiFERON TB Gold (QFT-IT antigens) decreases after successful TB therapy. The objective of this study was to evaluate whether there are factors other than IFN-γ [such as IFN-γ inducible protein (IP)-10 which has also been associated with TB] in response to QFT-IT antigens that can be used as biomarkers for monitoring TB treatment.

Methods: In this exploratory study we assessed the changes in IP-10 secretion in response to QFT-IT antigens and RD1 peptides selected by computational analysis in 17 patients with active TB at the time of diagnosis and after 6 months of treatment. The IFN-γ response to QFT-IT antigens and RD1 selected peptides was evaluated as a control. A non-parametric Wilcoxon signed-rank test for paired comparisons was used to compare the continuous variables at the time of diagnosis and at therapy completion. A Chi-square test was used to compare proportions.

Results: We did not observe significant IP-10 changes in whole blood from either NIL or QFT-IT antigen tubes, after 1-day stimulation, between baseline and therapy completion (p = 0.08 and p = 0.7 respectively). Conversely, the level of IP-10 release to RD1 selected peptides was significantly different (p = 0.006). Similar results were obtained when we detected the IFN-γ in response to the QFT-IT antigens (p = 0.06) and RD1 selected peptides (p = 0.0003). The proportion of the IP-10 responders to the QFT-IT antigens did not significantly change between baseline and therapy completion (p = 0.6), whereas it significantly changed in response to RD1 selected peptides (p = 0.002). The proportion of IFN-γ responders between baseline and therapy completion was not significant for QFT-IT antigens (p = 0.2), whereas it was significant for the RD1 selected peptides (p = 0.002), confirming previous observations.

Conclusions: Our preliminary study provides an interesting hypothesis: IP-10 response to RD1 selected peptides (similar to IFN-γ) might be a useful biomarker for monitoring therapy efficacy in patients with active TB. However, further studies in larger cohorts are needed to confirm the consistency of these study results.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology*
  • Antitubercular Agents / therapeutic use*
  • Biomarkers / blood
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / immunology*
  • Drug Monitoring / methods*
  • Female
  • Humans
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / isolation & purification
  • Prospective Studies
  • Tuberculosis / blood
  • Tuberculosis / drug therapy*
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology
  • Young Adult

Substances

  • Antigens, Bacterial
  • Antitubercular Agents
  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Interferon-gamma