Novel blood biomarkers distinguish active pulmonary tuberculosis from non-pulmonary tuberculosis: a prospective, large scale, clinical trial in Eastern China.

OBJECTIVES: Active Tuberculosis (TB) had the challenge in early detection. Our pilot study showed four novel diagnostic biomarkers had high value of TB diagnosis. The aim of the study was to further verify the diagnosis value of these biomarkers for active pulmonary TB (PTB) from non-TB through clinical trial with large scale samples. METHODS: The prospective, large scale, multicenter, diagnostic clinical trial was performed from 2022 Jan to 2024 Dec in Eastern China. PTB suspects met inclusion criteria were enrolled the study, taken RNA abstract from the Peripheral venous blood for RNA examination of BATF2, UBE2L6, SERPING1, VAMP5 and tested by QFT-GIT as well, the diagnosis value of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and AUC for active TB by single and fixed groups of biomarkers were calculated and evaluated. RESULTS: 890 cases were finally included the study, containing 564 cases of PTB (365 had definite and 199 had probable TB) and 326 cases of non-PTB. Any single biomarker from BATF2, UBE2L6, SERPNG1 or VAMP5 has advantage diagnosis values over QFT-GIT, UBE2L6 had the best value of the diagnosis (AUC 0.84) of active TB. Combination of UBE2L6/SERPING1/VAMP5 had best diagnosis value of active PTB (sensitivity of 70.5% and specificity of 95.4%) from non-PTB. CONCLUSIONS: Blood derived transcription level of combination on Three-genes (UBE2L6, SERPING1, VAMP5) had excellent diagnosis value of active PTB from non-TB diseases, which deserved clinical application in the future.