title: Identification of Novel RD1 Antigens and Their Combinations for Diagnosis of Sputum Smear-/Culture+ TB Patients.
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.
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Qie
authors.affiliation: Institute for Medical Devices Control, National Institute for Food and Drug Control, No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Bingshui
authors.initials: B
authors.lastname: Xiu
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Xiqin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Cuimi
authors.initials: C
authors.lastname: Duan
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Que
authors.affiliation: Chaoyang District Centre for Disease Control and Prevention, 25 Panjiayuan Huaweili, Beijing 100029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Olympia Diagnostics, Inc., 640 W. California Avenue, Sunnyvale, CA 94086, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Johnson
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Heqiu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Bio-Diagnosis, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Feng
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology / Q000302:isolation & purification*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D007074:Immunoglobulin G; C527546:rv3879c antigen, Mycobacterium tuberculosis