title: Profiling antibodies to Mycobacterium tuberculosis by multiplex microbead suspension arrays for serodiagnosis of tuberculosis.
abstract: Tuberculosis (TB) is a serious global disease. The fatality rate attributed to TB is among the highest of infectious diseases, with approximately 2 million deaths occurring per year worldwide. Identification of individuals infected with Mycobacterium tuberculosis and screening of their immediate contacts is crucial for controlling the spread of TB. Current methods for detection of M. tuberculosis infection are not efficient, in particular, for testing large numbers of samples. We report a novel and efficient multiplex microbead immunoassay (MMIA), based on Luminex technology, for profiling antibodies to M. tuberculosis. Microbead sets identifiable by unique fluorescence were individually coated with each of several M. tuberculosis antigens and tested in multiplex format for antibody detection in the experimental nonhuman primate model of TB. Certain M. tuberculosis antigens, e.g., ESAT-6, CFP-10, and HspX, were included to enhance the specificity of the MMIA, because these antigens are absent in nontuberculous mycobacteria and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin. The MMIA enabled simultaneous detection of multiple M. tuberculosis plasma antibodies in several cohorts of macaques representing different stages of infection and/or disease. Antibody profiles were defined in early and latent/chronic infection. These proof-of-concept findings demonstrate the potential clinical use of the MMIA. In addition, the MMIA serodetection system has a potential for mining M. tuberculosis open reading frames (about 4,000) to discover novel target proteins for the development of more-comprehensive TB serodiagnostic tests.
authors: Center for Comparative Medicine, Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, California 95616, USA. ihkhan@ucdavis.edu
authors: Imran H
authors: IH
authors: Khan
authors: Resmi
authors: R
authors: Ravindran
authors: JoAnn
authors: J
authors: Yee
authors: Melanie
authors: M
authors: Ziman
authors: David M
authors: DM
authors: Lewinsohn
authors: Marila L
authors: ML
authors: Gennaro
authors: JoAnne L
authors: JL
authors: Flynn
authors: Celia W
authors: CW
authors: Goulding
authors: Kathryn
authors: K
authors: DeRiemer
authors: Nickolas W
authors: NW
authors: Lerche
authors: Paul A
authors: PA
authors: Luciw
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D005453:Fluorescence; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology
chemical_list: D000914:Antibodies, Viral; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C118127:HspX protein, Mycobacterium tuberculosis