A TB antigen-stimulated CXCR3 ligand assay for the diagnosis of active pulmonary TB.

Abstract

BACKGROUND: The ligands for CXC chemokine receptor 3 (CXCR3) recruit T-helper

type 1 cells, which play a major role in cell-mediated immunity in TB. METHODS: A

total of 409 subjects were enrolled. The study population comprised 186 patients

with active TB, 58 patients with non-TB pulmonary diseases, 50 control subjects

with a positive interferon (IFN)-gamma release assay (IGRA) result, and 115

control subjects with a negative IGRA result. Whole-blood samples were collected

using IGRA methodology. After incubation, plasma IFN-gamma levels and two CXCR3

ligands, IFN-inducible T-cell alpha-chemoattractant (I-TAC, CXCL11) and monokine

induced by IFN-gamma (MIG, CXCL9), were measured by enzyme-linked immunosorbent

assay. Receiver operating characteristic (ROC) analysis was performed.

Sensitivity and specificity were based on cutoff values selected to maximize the

Youden index. RESULTS: The TB antigen-stimulated levels of IFN-gamma, I-TAC, and

MIG were significantly increased in the active pulmonary TB group compared with

all other groups. From ROC analysis, for the diagnosis of active TB, I-TAC and

MIG outperformed IFN-gamma in all comparisons with the IGRA-positive and

-negative control groups and the non-TB pulmonary disease group. The areas under

the curve (95% CI) for differentiating active pulmonary TB from all other groups

were 0.893 (0.864-0.924) for IFN-gamma, 0.962 (0.946-0.978) for I-TAC, and 0.944

(0.922-0.965) for MIG. Sensitivity and specificity were 90.3% and 90.7%,

respectively, for I-TAC; 92.5% and 85.2% for MIG; and 84.9% and 79.8% for

IFN-gamma. CONCLUSIONS: TB antigen-stimulated assays of I-TAC and MIG may be

useful surrogate markers in the diagnosis of active pulmonary TB.