Differential diagnostic value of simultaneous detection of CD69 and HLA-DR on host T and NK cells in QFT-TB assay for identifying active tuberculosis

Background

Interferon-gamma release assay (IGRA) for tuberculosis (TB) remains limited in its ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Activation markers on host T and NK cells are currently considered to be promising markers in the diagnosis of ATB.

Methods

This prospective observational study enrolled 213 participants and the participants were divided into ATB, LTBI, other lung-related diseases (ORD), and health control (HC) groups. CD69 and HLA-DR on T and NK cells were detected in QFT-TB assay, and a composite scoring system (TB-Flow) was created for the diagnosis of ATB.

Results

The expression of activation markers (CD69 and HLA-DR) were significantly increased in ATB. HLA-DR on NK cells, CD69 on T cells, and QFT-TB in the differential diagnosis of ATB and HC were all of good diagnostic value (AUC>0.90). In addition, the TB-Flow greatly improved the efficiency of differential diagnosis between ATB and LTBI (AUC=0.90, 95%CI: 0.84–0.96), with sensitivity and specificity of 79.17 % (95%CI: 64.60%–89.04 %) and 88.68 % (95%CI: 76.28%–95.31 %).

Conclusions

CD69 and HLA-DR on host T and NK cells are promising markers in distinguishing different TB infection status. Our blood-based TB-Flow scoring system can distinguish ATB from LTBI with good diagnostic efficacy.