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Original Research: Chest Infections |

A TB Antigen-Stimulated CXCR3 Ligand Assay for the Diagnosis of Active Pulmonary TBCXCR3 Ligand Assay in Pulmonary TB

Wou Young Chung, MD; Keu Sung Lee, MD; Yun Jung Jung, MD; Hye Lim Lee, MS; Young Sun Kim, PhD; Joo Hun Park, MD, PhD; Seung Soo Sheen, MD; Kwang Joo Park, MD, PhD
Author and Funding Information

From the Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.

CORRESPONDENCE TO: Kwang Joo Park, MD, PhD, Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon 443-721, South Korea; e-mail: parkkj@ajou.ac.kr


FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(2):283-291. doi:10.1378/chest.13-1855
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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)-γ 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-γ levels and two CXCR3 ligands, IFN-inducible T-cell α-chemoattractant (I-TAC, CXCL11) and monokine induced by IFN-γ (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-γ, 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-γ 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-γ, 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-γ.

CONCLUSIONS:  TB antigen-stimulated assays of I-TAC and MIG may be useful surrogate markers in the diagnosis of active pulmonary TB.

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