Clinical evaluation of diagnostic potential of several biomarkers for immunodiagnosis of tuberculosis infection including IGRAs

Abstract

Purpose: We focused on some cytokines and chemikines, suspecting a relationship with tuberculosis (TB) infection, and compared their usefulness for the diagnosis of TB infection with previous IGRAs. Materials and Methods: the subjects consisted of 46 patients with TB disease, 50 patients with pulmonary NTM disease (MAC: 48, M.abscessus: 2), and 16 patients with other pulonary diseases. We measured two IGRAs (QFT and T-SPOT.TB) using peripheral blood, and cytokines such as IL-2 and TNF-α or chemokines such as IP-10, MIG, and MCP-1 using the supernatant stimulated by QFT antigens in all patients. Results: In the TB group, while the positive response rates were 80% for QFT and 87% for T-SPOT.TB, they were 89% for IP-10, 87% for MIG, 80% for MCP-1, and 70% for IL-2 and TNF-α. In the patients in the NTM group, while the positive response rates of IGRAswere 8% for QFT and T-SPOT.TB, they were 10% for IP=10, 12% for MIG, 20% for MCP-2, and 32% for IL-2 and TNF-α. In the patients with other respiratory diseases, while the positive response rates were 19% for QFT and T-SPOT.TB, they were 13% for IP-10, 19% for MIG, 25% for MCP-1, and 38% for IL-2 and TNF-α. The combination of the diagnostic methods, such as the two IGRAs, IP-10, and MIG, increased the positive response rate to 93%. Conclusions: The Mycobacterium tuberculosis (MTB)-specific antigen-stimulated expression of the two chemikines related to IFN-γ (IP-10 and MIG) may be useful for detecting TB. Cobining the IGRAs with IP-10 and MIG could increase the detection rate of active TB disease over that using IGRAs alone.