Serum CXCR3 ligands as biomarkers for the diagnosis and treatment monitoring of tuberculosis

Int J Tuberc Lung Dis. 2015 Dec;19(12):1476-84. doi: 10.5588/ijtld.15.0325.

Abstract

Setting: Tertiary care academic medical centre.

Objective: To evaluate the clinical utility of CXC chemokine receptor 3 (CXCR3) ligands in the diagnosis and monitoring of tuberculosis (TB).

Design: Presumptive TB patients (active TB, 256; non-TB disease, 52) and 201 healthy controls were enrolled. The serum levels of interferon-gamma (IFN-γ) and CXCR3 ligands (CXCL9, a monokine induced by IFN-γ [MIG] and CXCL11, an IFN-inducible T-cell α chemoattractant [I-TAC]) were measured using enzyme-linked immunosorbent assay. An IFN-γ release assay (IGRA) was also performed. Serial samplings were performed in 19 TB patients at baseline and at 1, 2, 3, 6 and 12 months after treatment initiation.

Results: All marker levels were higher in TB patients than in controls and non-TB patients. The area under the curve (AUC) for differentiating between all TB patients and controls was 0.96 (95%CI 0.94-0.98) for CXCL9, 0.84 (95%CI 0.80-0.87) for CXCL11 and 0.61 (95%CI 0.57-0.66) for IFN-γ. CXCL9 levels afforded particularly high discriminatory power between TB patients and IGRA-positive controls (AUC = 0.95, 95%CI 0.92-0.97). The levels of CXCR3 ligands decreased significantly during follow-up, and these changes were correlated with treatment response.

Conclusion: CXCR3 ligands CXCL9 and CXCL11 may be useful surrogate markers for the diagnosis and follow-up of TB.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Chemokine CXCL11 / blood*
  • Chemokine CXCL9 / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interferon-gamma / blood*
  • Logistic Models
  • Male
  • Middle Aged
  • ROC Curve
  • Receptors, CXCR3 / metabolism
  • T-Lymphocytes / immunology*
  • Tuberculosis / blood
  • Tuberculosis / diagnosis*

Substances

  • Biomarkers
  • CXCL11 protein, human
  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL11
  • Chemokine CXCL9
  • IFNG protein, human
  • Receptors, CXCR3
  • Interferon-gamma