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Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring.

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring.
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Liu C, Zhao Z, Fan J, Lyon CJ, Wu HJ, Nedelkov D, Zelazny AM, Olivier KN, Cazares LH, Holland SM, Graviss EA, Hu Y,


Liu C, Zhao Z, Fan J, Lyon CJ, Wu HJ, Nedelkov D, Zelazny AM, Olivier KN, Cazares LH, Holland SM, Graviss EA, Hu Y, (click to view)

Liu C, Zhao Z, Fan J, Lyon CJ, Wu HJ, Nedelkov D, Zelazny AM, Olivier KN, Cazares LH, Holland SM, Graviss EA, Hu Y,

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Proceedings of the National Academy of Sciences of the United States of America 2017 03 27114(15) 3969-3974 doi 10.1073/pnas.1621360114

Abstract

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 Mycobacterium tuberculosis (Mtb) infections in clinically diverse populations and quickly assess Mtb treatment responses for emerging drug-resistant strains. We have identified Mtb-specific peptide fragments and developed a method 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. NanoDisk-MS diagnosed active Mtb cases with high sensitivity and specificity in a case-control study with cohorts reflecting the complexity of clinical practice. 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 HIV-positive patients significantly outperformed those reported for other available assays. NanoDisk-MS also exhibited high specificity (87.1-100%) in both healthy and high-risk groups. Absolute quantification of serum Mtb antigen concentration was informative in assessing responses to antimycobacterial treatment. Thus, a NanoDisk-MS assay approach could significantly improve the diagnosis and management of active TB cases, and perhaps other infectious diseases as well.

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