title: Quantification of circulatingMycobacterium tuberculosisantigen 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 activeMycobacterium tuberculosis(Mtb) infections in clinically diverse populations and quickly assessMtbtreatment responses for emerging drug-resistant strains. We have identifiedMtb-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 activeMtbcases 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 serumMtbantigen 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.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030.|School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287.|Virginia G. Piper Biodesign Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030.|Virginia G. Piper Biodesign Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030.|Virginia G. Piper Biodesign Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lyon
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030.|Department of Chemical Engineering, Texas A&M University, College Station, TX 77843.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Wu
authors.affiliation: Molecular Biomarkers Laboratory, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.
authors.forename: Dobrin
authors.initials: D
authors.lastname: Nedelkov
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Zelazny
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.affiliation: Molecular and Translational Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Cazares
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Graviss
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030; tyhu@asu.edu.|School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287.|Virginia G. Piper Biodesign Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006679:HIV Seropositivity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D053758:Nanoparticles; D010455:Peptides / Q000097:blood; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000295:instrumentation / Q000379:methods; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D010455:Peptides; C072681:Mycobacterium tuberculosis antigens
keywords: blood test; nanodisk; rapid diagnosis; treatment monitoring; tuberculosis