Muons penetrate much further than X-rays, they do essentially zero damage, and they are provided for free by the cosmos.
Image credit: Science Source/Digital Globe.
Edited by William R. Jacobs Jr., Albert Einstein College of Medicine, Howard Hughes Medical Institute, Bronx, NY, and approved February 17, 2017 (received for review January 6, 2017)
Significance
Active Mycobacterium tuberculosis (Mtb) infections represent a significant global health threat, but can be difficult to diagnose and manage owing to the nonquantitative nature and relatively poor performance of current frontline sputum-based diagnostic assays, which can be further degraded by certain Mtb manifestations. This study describes the development of a rapid and quantitative blood-based assay with high sensitivity and specificity for active Mtb infections that can be used to monitor responses to antimycobacterial therapy. Our method combines antibody-labeled, energy-focusing nanodisks with high-throughput mass spectrometry to enhance the detection of Mtb-specific peptides in digested serum samples, and should allow rapid clinical translation. This approach also should be applicable to other infectious diseases, particularly those for which conventional immunoassays exhibit suboptimal performance.
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.
Footnotes
- ↵1To whom correspondence should be addressed. Email: tyhu{at}asu.edu.
Author contributions: C.L., Z.Z., and Y.H. designed research; C.L., J.F., H.-J.W., and D.N. performed research; E.A.G. contributed clinical samples; C.L., Z.Z., J.F., C.J.L., A.M.Z., K.N.O., L.H.C., S.M.H., E.A.G., and Y.H. analyzed data; and C.L., Z.Z., C.J.L., A.M.Z., L.H.C., S.M.H., E.A.G., and Y.H. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1621360114/-/DCSupplemental.
Freely available online through the PNAS open access option.
TB diagnosis and therapy analysis by serum antigen
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
One protein seems to play a key role in touch sensitivity for flytraps and other meat-eating plants.
Image credit: Shutterstock/Kuttelvaserova Stuchelova.
Adam Mastroianni and Daniel Gilbert explore why conversations almost never end when people want them to.
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.