Circulating TB Antigens Allows Rapid Diagnosis of Active Disease

A rapid and quantitative blood-based assay with high sensitivity and specificity for active Mycobacterium tuberculosis (Mtb) infections has been developed that can be used to monitor responses to anti-mycobacterial therapy.

Tuberculosis (TB) is a major global health threat, resulting in an urgent unmet need for a rapid, non–sputum-based quantitative test to detect active Mtb infections in clinically diverse populations and quickly assess Mtb treatment responses for emerging drug-resistant strains.


A team of scientists led by those at the Arizona State University’s Biodesign Institute have identified Mtb-specific peptide fragments and developed a method called NanoDisk-MS, to rapidly quantify their serum concentrations, using antibody-labeled and energy-focusing porous discoidal silicon nanoparticles (nanodisks) and high-throughput mass spectrometry (MS) to enhance sensitivity and specificity.

The scientists found that NanoDisk-MS diagnosed active Mtb cases with high sensitivity and specificity in a case-control study with cohorts reflecting the complexity of clinical practice. It does so by accurately detecting minute blood levels of two proteins: 10-kDa culture filtrate protein (CFP-10) and 6-kDa early secretory antigenic target (ESAT-6) that Mtb release only during active infections. Similar robust sensitivities were obtained for cases of culture-positive pulmonary TB (PTB; 91.3%) and extrapulmonary TB (EPTB; 92.3%), and the sensitivities obtained for culture-negative PTB (82.4%) and EPTB (75.0%) in human immunodeficiency virus (HIV)-positive patients significantly outperformed those reported for other available assays. NanoDisk-MS also exhibited high specificity (87.1% to 100%) in both healthy and high-risk groups. Absolute quantification of serum Mtb antigen concentration was informative in assessing responses to anti-mycobacterial treatment.

Tony Ye Hu, PhD, an associate professor and lead author of the study said, “In the current frontlines of TB testing, coughed-up sputum, blood culture tests, invasive lung and lymph biopsies, or spinal taps are the only way to diagnose TB. The results can give false negatives, and these tests are further constrained because they can take days to weeks to get the results. We are particularly excited about the ability of our high-throughput assay to provide rapid quantitative results that can be used to monitor treatment effects, which will give physicians the ability to better treat worldwide TB infections.” The study was published on March 27, 2017, in the journal Proceedings of the National Academy of Sciences.