QuantiFERON-TB Gold Plus combined with HBHA-Induced IFN-γ release assay improves the accuracy of identifying tuberculosis disease status. (September 2020)

• Record Type: Journal Article
• Authors: Tang, Jinhua; Huang, Yuan; Jiang, Shen; Huang, Fang; Ma, Tingting; Qi, Yun; Ma, Yueyun
• Is Part Of: Tuberculosis. Volume 124(2020)
• Publication Date: 2020-09
• Subjects: IGRA -- QFT-Plus -- HBHA -- Active TB -- LTBI; 616.995
• DOI: 10.1016/j.tube.2020.101966
• Languages: English
• ISSNs: 1472-9792

Abstract

Abstract: Objective: QFT-Plus's newly added antigen elicited a specific CD8 T-cell response, which is closely related to active TB (ATB), and the IGRA based on Heparin-binding haemagglutinin (HBHA-IGRA) is a promising tool in latent tuberculosis infection (LTBI) diagnosis. The objective of our study is to evaluate whether the combination of QFT-Plus and HBHA-IGRA can improve the diagnosis accuracy of ATB and LTBI. Methods: 135 healthcare workers (HCWs) and 57 patients with active pulmonary TB in a Chinese TB Hospital were recruited, HCWs underwent screening for LTBI using the QFT-Plus assay. Flow cytometry was used to analyze the distribution of peripheral blood T lymphocyte subsets in active TB patients with positive culture result. Then, the patients with ATB, individuals with LTBI and healthy TB-uninfected controls (HC) were tested by QFT-Plus and HBHA-IGRA respectively, and the efficiency of distinguishing LTBI from ATB by QFT-Plus and HBHA-IGRA were evaluated by Receiver Operating Characteristic (ROC) curves. Results: QFT-Plus TB2-TB1 which was positively correlated with CD8 T-cell response (r = 0.731, P < 0.001) in peripheral blood was significantly higher in ATB than LTBI and HC (median 0.47 IU/mL versus 0.02 IU/mL and 0.00 IU/mL, respectively; both P < 0.0001). While the HBHA-induced IFN-γ response did not differ between ATB and HC (median 12.12 pg/mL versus 10.95 pg/mL; P = 0.463), but was significantly higher in the LTBI (median 69.67 pg/mL; both P < 0.0001). The ROC area under the curve (AUC) for identifying ATB and LTBI was 0.769 (95% CI: 0.652–0.886; P = 0.0001) for QFT-Plus TB2-TB1, and 0.886 (95% CI:0.791–0.982; P＜0.0001) for HBHA-IGRA. After combining the HBHA-IGRA with QFT-Plus results, the accuracy of identifying ATB and LTBI was improved to 85.7% from 74.3%. Conclusions: HBHA-based IGRA better differentiates between LTBI and ATB compared to QFT-Plus CD8 T-cell response. In addition, combining HBHA-IGRA and QFT-Plus improves the accuracy of identifying tuberculosis disease status. Highlights: QFT-Plus TB2-TB1 was positively correlated with CD8 response in peripheral blood. QFT-Plus CD8 response was significantly higher in active TB than LTBI individuals. HBHA-IGRA was significantly higher in LTBI individuals than active TB patients. HBHA-IGRA better discriminates LTBI and active TB compared to QFT-Plus CD8 response. Combining HBHA-IGRA and QFT-Plus improves the accuracy of identifying TB status.