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BioMed Research International
Volume 2016 (2016), Article ID 7486425, 10 pages
http://dx.doi.org/10.1155/2016/7486425
Research Article

Identification of Novel RD1 Antigens and Their Combinations for Diagnosis of Sputum Smear−/Culture+ TB Patients

1Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China
2Institute for Medical Devices Control, National Institute for Food and Drug Control, No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China
3Chaoyang District Centre for Disease Control and Prevention, 25 Panjiayuan Huaweili, Beijing 100029, China
4Olympia Diagnostics, Inc., 640 W. California Avenue, Sunnyvale, CA 94086, USA

Received 22 July 2015; Revised 30 September 2015; Accepted 4 November 2015

Academic Editor: Aparup Das

Copyright © 2016 Zhiqiang Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Rapid and accurate diagnosis of pulmonary tuberculosis (PTB) is an unresolved problem worldwide, especially for sputum smear− (S−) cases. In this study, five antigen genes including Rv3871, Rv3874, Rv3875, Rv3876, and Rv3879 were cloned from Mycobacterium tuberculosis (Mtb) RD1 and overexpressed to generate antigen fragments. These antigens and their combinations were investigated for PTB serodiagnosis. 298 serum samples were collected from active PTB patients, including 117 sputum smear+ (S+) and sputum culture+ (C+) cases, 101 S−/C+ cases, and 80 S−/C− cases. The serum IgG levels of the five antigens were measured by ELISA. Based on IgG levels, the sensitivity/specificity of Rv3871, Rv3874, Rv3875, Rv3876, and Rv3879 for PTB detection was 81.21%/74.74%, 63.09%/94.78%, 32.21%/87.37%, 62.42%/85.26%, and 83.56%/83.16%, respectively. Furthermore, the optimal result for PTB diagnosis was achieved by combining antigens Rv3871, Rv3876, and Rv3879. In addition, the IgG levels of Rv3871, Rv3876, and Rv3879 were found to be higher in S−/C+ PTB patients than in other PTB populations. More importantly, combination of the three antigens demonstrated superior diagnostic performance for both S−/C+ and S−/C− PTB. In conclusion, the combination of Rv3871, Rv3876, and Rv3879 induced higher IgG response in sputum S−/C+ PTB patients and represents a promising biomarker combination for diagnosing of PTB.