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

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.

• Authors: Chang Liu, Zhen Zhao, Jia Fan, Christopher J Lyon, Hung-Jen Wu, Dobrin Nedelkov, Adrian M Zelazny, Kenneth N Olivier, Lisa H Cazares, Steven M Holland, Edward A Graviss, Ye Hu
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 114 Issue 15 Pg. 3969-3974 (Apr 11 2017) ISSN: 1091-6490 [Electronic] United States
• PMID: 28348223 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• CFP-10 protein, Mycobacterium tuberculosis
• ESAT-6 protein, Mycobacterium tuberculosis
• Peptides
• Mycobacterium tuberculosis antigens

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Bacterial (blood)
• Bacterial Proteins (blood)
• Case-Control Studies
• Female
• HIV Seropositivity
• Humans
• Male
• Middle Aged
• Mycobacterium tuberculosis (pathogenicity)
• Nanoparticles
• Peptides (blood)
• Sensitivity and Specificity
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (instrumentation, methods)
• Tuberculosis (diagnosis, drug therapy, microbiology)
• Tuberculosis, Pulmonary (diagnosis, drug therapy, microbiology)