Abstract
Bacterial culture of M. tuberculosis (MTB), the causative agent of tuberculosis (TB), from clinical specimens is the gold standard for laboratory diagnosis of TB, but is slow and culture-negative TB cases are common. Alternative immune-based and molecular approaches have been developed, but cannot discriminate between active TB (ATB) and latent TB (LTBI). Here, to identify biomarkers that can discriminate between ATB and LTBI/healthy individuals (HC), we profiled 116 serum samples (HC, LTBI and ATB) using a protein microarray containing 257 MTB secreted proteins, identifying 23 antibodies against MTB antigens that were present at significantly higher levels in patients with ATB than in those with LTBI and HC (Fold change > 1.2; p < 0.05). A 4-protein biomarker panel (Rv0934, Rv3881c, Rv1860 and Rv1827), optimized using SAM and ROC analysis, had a sensitivity of 67.3% and specificity of 91.2% for distinguishing ATB from LTBI, and 71.2% sensitivity and 96.3% specificity for distinguishing ATB from HC. Validation of the four candidate biomarkers in ELISA assays using 440 serum samples gave consistent results. The promising sensitivity and specificity of this biomarker panel suggest it merits further investigation for its potential as a diagnostic for discriminating between latent and active TB.
Highlights
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is the leading cause of death from infectious diseases[1]
We identified a panel of 4 proteins with high sensitivity and specificity that could distinguish active tuberculosis (ATB) from LTBI, and verified the performance of these four proteins using enzyme-linked immunosorbent assay (ELISA) assays and 440 serum samples
I.e. proteins present at different levels in samples from ATB patients and those from individuals with LTBI or healthy individuals, promising candidate biomarkers were selected based on their sensitivity and specificity in the differential diagnosis of ATB
Summary
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is the leading cause of death from infectious diseases[1]. Serum biomarkers for TB, such as the 38kD, 16kD, ESAT-6, MPT63, 19kD, MPT64, MPT32, Rv1009, MTB48, Mtb[81], MTC28, Ag85B, and KatG proteins have been identified[19], but while most show high sensitivity in ATB patients[20], their sensitivity and specificity is insufficient for discriminating between active TB and LTBI21. We identified a panel of 4 proteins with high sensitivity and specificity that could distinguish ATB from LTBI, and verified the performance of these four proteins using ELISA assays and 440 serum samples. This panel merits further investigation for its potential in diagnosing active pulmonary tuberculosis
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