Evaluation of the diagnostic potential of IP-10 and IL-2 as biomarkers for the diagnosis of active and latent tuberculosis in a BCG-vaccinated population

PLoS One. 2012;7(12):e51338. doi: 10.1371/journal.pone.0051338. Epub 2012 Dec 14.

Abstract

Background: The Mycobacterium tuberculosis (Mtb)-specific T-cell interferon gamma release assays (IGRAs) are useful in detecting Mtb infection but perform poorly at distinguishing active tuberculosis disease (ATB) and latent tuberculosis infection (LTBI). This study is aimed at evaluating additional cytokines as biomarkers besides interferon-gamma (IFN-γ) to improve the identification of ATB and LTBI.

Methodology/principal findings: Sixty-six patients with ATB, 73 household contacts (HHC) of ATB patients and 76 healthy controls (HC) were recruited to undergo QuantiFERON TB GOLD in-tube assay (QFT) and the enzyme-linked immunosorbent assay (ELISA) where the release of IFN-γ, IFN-γ inducible protein 10 (IP-10), Interleukin 2 (IL-2) and Tumor Necrosis Factor-α (TNF-α) was determined in the whole blood with or without antigen-stimulation. The positive rates of the QFT, IP-10 and IL-2 tests were 86.4%, 89.4% and 86.4% for the ATB group with no difference between them (p>0.05). However, QFT in combination with IP-10 and IL-2 significantly increased the detection rate to 95.5% in the ATB group (p = 0.03) and the indeterminate rate of all samples decreased from 2.3% (5/215) to 0.4% (1/215). The un-stimulated level of IP-10 was significantly higher in the HHC than the ATB and HC groups. The IP-10 responses were strongly associated with extended Mtb exposure time and the degree of smear-positivity of the index cases. The IL-2/IFN-γ ratio in the antigen-stimulated plasma could discriminate LTBI from ATB with a sensitivity of 77.2% and a specificity of 87.2%.

Conclusion: The increased Mtb-specific antigen-stimulated expression of IP-10 and IL-2 may be useful for detecting both ATB and LTBI. Combining the QFT with IP-10 and IL-2 could increase the detection accuracy of active TB over the QFT alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens / metabolism
  • BCG Vaccine / metabolism*
  • Biomarkers / metabolism
  • Chemokine CXCL10 / blood*
  • Cross-Sectional Studies
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / blood*
  • Latent Tuberculosis / blood*
  • Male
  • Middle Aged
  • Sensitivity and Specificity
  • T-Lymphocytes / metabolism
  • Time Factors
  • Tuberculin Test
  • Tuberculosis / blood*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens
  • BCG Vaccine
  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Cytokines
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma

Grant support

This work was supported by research grants from the Key Technologies Research and Development Program for Infectious Diseases of China (2013ZX10003001-002), Shanghai Science and Technology Development Funds (10XD1400900, 10QA1401100), National Natural Science Foundation of China (30901277) and the Key Project of Science and Technology of Shanghai (10411955000). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.