IP-10 and MIG Are Compartmentalized at the Site of Disease during Pleural and Meningeal Tuberculosis and Are Decreased after

The diagnosis of active tuberculosis (TB) disease remains a challenge, especially in high-burden settings. Cytokines and chemo-kines are important in the pathogenesis of TB. Here we investigate the usefulness of circulating and compartmentalized cyto-kines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF), and cerebrospi-nal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 andMIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG for distinguishing TB from LTBI. However, IP-10 andMIG levels in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 andMIG in the PF and CSF showed promising diagnostic values in discrimi-nating TB and non-TB pleural effusion (AUC 0.87 for IP-10 and 0.93 for MIG), as well as TBmeningitis and non-TBmeningi-tis (AUC 0.9 for IP-10 and 0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, granulocyte colony-stimulating factor (G-CSF), and gamma interferon (IFN-) decreased, while the levels of MCP-1/CCL2 and eotaxin-1/ CCL11 increased, after successful treatment of TB. Our findings provide a practical methodology for discriminating active TB from LTBI by sequential IFN- release assays (IGRAs) and plasma IP-10 testing, while increased IP-10 andMIG at the site of infection (PF or CSF) can be used as a marker for distinguishing pleural effusion andmeningitis caused by TB from those o