9 and 21 Levels of IFN-γ, IL-2, and CXCL10 in QFT-IT supernatant were significantly higher in TB patients than in normal controls whereas
none of the 3 analytes clearly differentiated between TB and LTBI as previously reported. 9, 22 and 23 These data indicate that assessment of a combination of IL-2 and CXCL10 may enhance the sensitivity of IGRA that measures only IFN-γ levels for diagnosis of M. tb infection. In addition, serum VEGF-A concentrations may serve as a biomarker to discriminate TB from LTBI. The relatively low specificity of serum VEGF-A concentrations may be improved by the combined measurement of IFN-γ, IL-2 and CXCL10 in response to M. tb antigens. Molecular tests have high specificity and sensitivity for rapid diagnosis and differentiation between pulmonary TB and NTM diseases, 5 and 6 but our data also provide a panel of serum cytokines CP-868596 molecular weight (IL-2, IL-9, IL-13, IL-17, TNF-α and sCD40L) for differential diagnosis of active TB and NTM (P < 0.01). This panel may aid in early diagnosis prior to identification of clinical isolates by culture. CD40L (CD154) is a co-stimulatory molecule that plays a role in enhancing cell-mediated immunity to intracellular pathogens by inducing IL-12, which subsequently generates Th1-type cytokines through interactions with CD40 on macrophages check details or dendritic cells.24 Defective CD40L expression in PBMCs from TB patients contributes
to decreased IFN-γ production by PBMCs.25 Significantly higher levels of plasma sCD40L is present in plasma from TB patients in the fifth week of anti-TB treatment compared to pre-treatment,7 which is consistent with our findings. However, sCD40L
responses did not change significantly in response to M. tb antigens. It has been suggested that the IGRA is not appropriate as a monitoring tool for anti-TB treatment due to the substantial proportion of patients with positive QFT-IT (46%) and T-SPOT.TB® (79%) results after TB treatment. 26 There was no difference in IP-10 levels of QFT-IT plasma between pre- and post-treatment whereas significant changes in IP-10 release were observed in response to RD1 selected peptides (ESAT-6 and CFP-10). 27 Our study also showed no significant change in IP-10 levels of QFT-IT plasma between baseline and post-treatment. Meanwhile, science both the magnitude of IFN-γ responses and the proportion of the responders showing high IFN-γ production (>1000 pg/mL) were significantly reduced post-treatment (P < 0.001). Rapid decreases in TNF-α and IL-2 responses and the percentage of responders correlated with M. tb sputum conversion in culture after 2 months of treatment. These results suggest that screening levels of serum sCD40L together with M. tb antigen-specific IFN-γ, TNF-α, and IL-2 responses may help evaluate drug efficacy, particularly the early therapeutic effect, in TB patients. However, our findings of M.