RT Journal Article
SR Electronic
T1 Identification of eight-protein biosignature for diagnosis of tuberculosis
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 576
OP 583
DO 10.1136/thoraxjnl-2018-213021
VO 75
IS 7
A1 Qianting Yang
A1 Qi Chen
A1 Mingxia Zhang
A1 Yi Cai
A1 Fan Yang
A1 Jieyun Zhang
A1 Guofang Deng
A1 Taosheng Ye
A1 Qunyi Deng
A1 Guobao Li
A1 Huihua Zhang
A1 Yuhua Yi
A1 Ruo-Pan Huang
A1 Xinchun Chen
YR 2020
UL http://thorax.bmj.com/content/75/7/576.abstract
AB Background Biomarker-based tests for diagnosing TB currently rely on detecting Mycobacterium tuberculosis (Mtb) antigen-specific cellular responses. While this approach can detect Mtb infection, it is not efficient in diagnosing TB, especially for patients who lack aetiological evidence of the disease.Methods We prospectively enrolled three cohorts for our study for a total of 630 subjects, including 160 individuals to screen protein biomarkers of TB, 368 individuals to establish and test the predictive model and 102 individuals for biomarker validation. Whole blood cultures were stimulated with pooled Mtb-peptides or mitogen, and 640 proteins within the culture supernatant were analysed simultaneously using an antibody-based array. Sixteen candidate biomarkers of TB identified during screening were then developed into a custom multiplexed antibody array for biomarker validation.Results A two-round screening strategy identified eight-protein biomarkers of TB: I-TAC, I-309, MIG, Granulysin, FAP, MEP1B, Furin and LYVE-1. The sensitivity and specificity of the eight-protein biosignature in diagnosing TB were determined for the training (n=276), test (n=92) and prediction (n=102) cohorts. The training cohort had a 100% specificity (95% CI 98% to 100%) and 100% sensitivity (95% CI 96% to 100%) using a random forest algorithm approach by cross-validation. In the test cohort, the specificity and sensitivity were 83% (95% CI 71% to 91%) and 76% (95% CI 56% to 90%), respectively. In the prediction cohort, the specificity was 84% (95% CI 74% to 92%) and the sensitivity was 75% (95% CI 57% to 89%).Conclusions An eight-protein biosignature to diagnose TB in a high-burden TB clinical setting was identified.