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

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.