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Clinical and Vaccine Immunology, March 2008, p. 433-438, Vol. 15, No. 3
1071-412X/08/$08.00+0     doi:10.1128/CVI.00354-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Profiling Antibodies to Mycobacterium tuberculosis by Multiplex Microbead Suspension Arrays for Serodiagnosis of Tuberculosis

Imran H. Khan,^1,2*, Resmi Ravindran,^1, JoAnn Yee,³ Melanie Ziman,¹ David M. Lewinsohn,⁵ Marila L. Gennaro,⁶ JoAnne L. Flynn,⁷ Celia W. Goulding,⁸ Kathryn DeRiemer,⁴ Nickolas W. Lerche,³ and Paul A. Luciw^1,2,3

Center for Comparative Medicine,¹ Department of Pathology and Laboratory Medicine,² California National Primate Research Center,³ School of Medicine, University of California, Davis, California 95616,⁴ Division of Pulmonary and Critical Care Medicine, Oregon Health and Sciences University, Portland, Oregon 97239,⁵ Public Health Research Institute, Newark, New Jersey 07103,⁶ Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15261,⁷ University of California, Irvine, California 91679⁸

Received 29 August 2007/ Returned for modification 20 September 2007/ Accepted 26 November 2007

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.

Published ahead of print on 12 December 2007.

I.H.K. and R.R. contributed equally.