Skip to main content
Top
Published in: BMC Infectious Diseases 1/2022

Open Access 01-12-2022 | Tuberculosis | Research

Whole blood GBP5 protein levels in patients with and without active tuberculosis

Authors: Xiangyang Yao, Wei Liu, Xiaofei Li, Chenxi Deng, Tingdong Li, Zhouyue Zhong, Shuping Chen, Zhitan Ge, Xuejie Zhang, Shiyin Zhang, Yingbin Wang, Yongliang Liu, Chao Zheng, Shengxiang Ge, Ningshao Xia

Published in: BMC Infectious Diseases | Issue 1/2022

Login to get access

Abstract

Background

The host blood transcriptional levels of several genes, such as guanylate binding protein 5 (GBP5), have been reported as potential biomarkers for active tuberculosis (aTB) diagnosis. The aim of this study was to investigate whole blood GBP5 protein levels in aTB and non-tuberculosis patients.

Methods

An in-house immunoassay for testing GBP5 protein levels in whole blood was developed, and suspected aTB patients were recruited. Whole blood samples were collected and tested at enrolment using interferon-gamma release assay (IGRA) and the GBP5 assay.

Results

A total of 470 participants were enrolled, and 232 and 238 patients were finally diagnosed with aTB and non-TB, respectively. The GBP5 protein levels of aTB patients were significantly higher than those of non-tuberculosis patients (p < 0.001), and the area under the ROC curve of the GBP5 assay for aTB diagnosis was 0.76. The reactivity of the GBP5 assay between pulmonary and extrapulmonary tuberculosis patients was comparable (p = 0.661). With the optimal cut-off value, the sensitivity and specificity of the GBP5 assay for diagnosing aTB were 78.02 and 66.81%, respectively, while those of IGRA were 77.59 and 76.47%. The combination of the GBP5 assay and IGRA results in 88.52% accuracy for diagnosing aTB in 63.83% of suspected patients with a positive predictive value of 89.57% and a negative predictive value of 87.59%.

Conclusions

Whole blood GBP5 protein is a valuable biomarker for diagnosing of aTB. This study provides an important idea for realizing the clinical application of whole blood transcriptomics findings by immunological methods.
Appendix
Available only for authorised users
Literature
3.
go back to reference Reid MJ, Shah NS. Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis. 2009;9(3):173–84.CrossRef Reid MJ, Shah NS. Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis. 2009;9(3):173–84.CrossRef
4.
go back to reference Lawn SD, Mwaba P, Bates M, Piatek A, Alexander H, Marais BJ, et al. Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test. Lancet Infect Dis. 2013;13(4):349–61.CrossRef Lawn SD, Mwaba P, Bates M, Piatek A, Alexander H, Marais BJ, et al. Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test. Lancet Infect Dis. 2013;13(4):349–61.CrossRef
5.
go back to reference Pai M, Behr MA, Dowdy D, Dheda K, Divangahi M, Boehme CC, et al. Tuberculosis. Nat Rev Dis Primers. 2016;2:16076.CrossRef Pai M, Behr MA, Dowdy D, Dheda K, Divangahi M, Boehme CC, et al. Tuberculosis. Nat Rev Dis Primers. 2016;2:16076.CrossRef
6.
go back to reference Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis. N Engl J Med. 2013;368(8):745–55.CrossRef Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis. N Engl J Med. 2013;368(8):745–55.CrossRef
7.
go back to reference Callaway E. Improved diagnostics fail to halt the rise of tuberculosis. Nature. 2017;551(7681):424–5.CrossRef Callaway E. Improved diagnostics fail to halt the rise of tuberculosis. Nature. 2017;551(7681):424–5.CrossRef
9.
go back to reference Pandey V, Singh P, Singh S, Arora N, Quadir N, Singh S, et al. SeeTB: A novel alternative to sputum smear microscopy to diagnose tuberculosis in high burden countries. Sci Rep. 2019;9(1):16371.CrossRef Pandey V, Singh P, Singh S, Arora N, Quadir N, Singh S, et al. SeeTB: A novel alternative to sputum smear microscopy to diagnose tuberculosis in high burden countries. Sci Rep. 2019;9(1):16371.CrossRef
10.
go back to reference Tan Y, Su B, Cai X, Guan P, Liu X, Ma P, et al. An automated smear microscopy system to diagnose tuberculosis in a high-burden setting. Clin Microbiol Infect. 2019;25(12):1553–9.CrossRef Tan Y, Su B, Cai X, Guan P, Liu X, Ma P, et al. An automated smear microscopy system to diagnose tuberculosis in a high-burden setting. Clin Microbiol Infect. 2019;25(12):1553–9.CrossRef
11.
go back to reference Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014;1:CD009593. Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014;1:CD009593.
12.
go back to reference Fan L, Li D, Zhang S, Yao L, Hao X, Gu J, et al. Parallel Tests Using Culture, Xpert MTB/RIF, and SAT-TB in sputum plus bronchial alveolar lavage fluid significantly increase diagnostic performance of smear-negative pulmonary tuberculosis. Front Microbiol. 2018;9:1107.CrossRef Fan L, Li D, Zhang S, Yao L, Hao X, Gu J, et al. Parallel Tests Using Culture, Xpert MTB/RIF, and SAT-TB in sputum plus bronchial alveolar lavage fluid significantly increase diagnostic performance of smear-negative pulmonary tuberculosis. Front Microbiol. 2018;9:1107.CrossRef
13.
go back to reference Hillemann D, Rusch-Gerdes S, Boehme C, Richter E. Rapid molecular detection of extrapulmonary tuberculosis by the automated GeneXpert MTB/RIF system. J Clin Microbiol. 2011;49(4):1202–5.CrossRef Hillemann D, Rusch-Gerdes S, Boehme C, Richter E. Rapid molecular detection of extrapulmonary tuberculosis by the automated GeneXpert MTB/RIF system. J Clin Microbiol. 2011;49(4):1202–5.CrossRef
14.
go back to reference Penz E, Boffa J, Roberts DJ, Fisher D, Cooper R, Ronksley PE, et al. Diagnostic accuracy of the Xpert(R) MTB/RIF assay for extra-pulmonary tuberculosis: a meta-analysis. Int J Tuberc Lung Dis. 2015;19(3):278–84, i-iii.CrossRef Penz E, Boffa J, Roberts DJ, Fisher D, Cooper R, Ronksley PE, et al. Diagnostic accuracy of the Xpert(R) MTB/RIF assay for extra-pulmonary tuberculosis: a meta-analysis. Int J Tuberc Lung Dis. 2015;19(3):278–84, i-iii.CrossRef
15.
go back to reference Sali M, Buonsenso D, D’Alfonso P, De Maio F, Ceccarelli M, Battah B, et al. Combined use of Quantiferon and HBHA-based IGRA supports tuberculosis diagnosis and therapy management in children. J Infect. 2018;77(6):526–33.CrossRef Sali M, Buonsenso D, D’Alfonso P, De Maio F, Ceccarelli M, Battah B, et al. Combined use of Quantiferon and HBHA-based IGRA supports tuberculosis diagnosis and therapy management in children. J Infect. 2018;77(6):526–33.CrossRef
16.
go back to reference Whitworth HS, Badhan A, Boakye AA, Takwoingi Y, Rees-Roberts M, Partlett C, et al. Clinical utility of existing and second-generation interferon-gamma release assays for diagnostic evaluation of tuberculosis: an observational cohort study. Lancet Infect Dis. 2019;19(2):193–202.CrossRef Whitworth HS, Badhan A, Boakye AA, Takwoingi Y, Rees-Roberts M, Partlett C, et al. Clinical utility of existing and second-generation interferon-gamma release assays for diagnostic evaluation of tuberculosis: an observational cohort study. Lancet Infect Dis. 2019;19(2):193–202.CrossRef
17.
go back to reference Sweeney TE, Braviak L, Tato CM, Khatri P. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med. 2016;4(3):213–24.CrossRef Sweeney TE, Braviak L, Tato CM, Khatri P. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med. 2016;4(3):213–24.CrossRef
18.
go back to reference Francisco NM, Fang YM, Ding L, Feng S, Yang Y, Wu M, et al. Diagnostic accuracy of a selected signature gene set that discriminates active pulmonary tuberculosis and other pulmonary diseases. J Infect. 2017;75(6):499–510.CrossRef Francisco NM, Fang YM, Ding L, Feng S, Yang Y, Wu M, et al. Diagnostic accuracy of a selected signature gene set that discriminates active pulmonary tuberculosis and other pulmonary diseases. J Infect. 2017;75(6):499–510.CrossRef
19.
go back to reference Yao X, Liu Y, Liu Y, Liu W, Ye Z, Zheng C, et al. Multiplex analysis of plasma cytokines/chemokines showing different immune responses in active TB patients, latent TB infection and healthy participants. Tuberculosis (Edinb). 2017;107:88–94.CrossRef Yao X, Liu Y, Liu Y, Liu W, Ye Z, Zheng C, et al. Multiplex analysis of plasma cytokines/chemokines showing different immune responses in active TB patients, latent TB infection and healthy participants. Tuberculosis (Edinb). 2017;107:88–94.CrossRef
20.
go back to reference Kaforou M, Wright VJ, Oni T, French N, Anderson ST, Bangani N, et al. Detection of tuberculosis in HIV-infected and -uninfected African adults using whole blood RNA expression signatures: a case-control study. PLoS Med. 2013;10(10):e1001538.CrossRef Kaforou M, Wright VJ, Oni T, French N, Anderson ST, Bangani N, et al. Detection of tuberculosis in HIV-infected and -uninfected African adults using whole blood RNA expression signatures: a case-control study. PLoS Med. 2013;10(10):e1001538.CrossRef
21.
go back to reference Roe JK, Thomas N, Gil E, Best K, Tsaliki E, Morris-Jones S, et al. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis. JCI Insight. 2016;1(16):e87238.CrossRef Roe JK, Thomas N, Gil E, Best K, Tsaliki E, Morris-Jones S, et al. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis. JCI Insight. 2016;1(16):e87238.CrossRef
22.
go back to reference Gjoen JE, Jenum S, Sivakumaran D, Mukherjee A, Macaden R, Kabra SK, et al. Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children. Sci Rep. 2017;7(1):5839.CrossRef Gjoen JE, Jenum S, Sivakumaran D, Mukherjee A, Macaden R, Kabra SK, et al. Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children. Sci Rep. 2017;7(1):5839.CrossRef
23.
go back to reference Laux da Costa L, Delcroix M, Dalla Costa ER, Prestes IV, Milano M, Francis SS, et al. A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases. Tuberculosis (Edinb). 2015;95(4):421–5.CrossRef Laux da Costa L, Delcroix M, Dalla Costa ER, Prestes IV, Milano M, Francis SS, et al. A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases. Tuberculosis (Edinb). 2015;95(4):421–5.CrossRef
25.
go back to reference Turner CT, Gupta RK, Tsaliki E, Roe JK, Mondal P, Nyawo GR, et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. Lancet Respir Med. 2020;8(4):407–19.CrossRef Turner CT, Gupta RK, Tsaliki E, Roe JK, Mondal P, Nyawo GR, et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. Lancet Respir Med. 2020;8(4):407–19.CrossRef
26.
go back to reference Krapp C, Hotter D, Gawanbacht A, McLaren PJ, Kluge SF, Sturzel CM, et al. Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity. Cell Host Microbe. 2016;19(4):504–14.CrossRef Krapp C, Hotter D, Gawanbacht A, McLaren PJ, Kluge SF, Sturzel CM, et al. Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity. Cell Host Microbe. 2016;19(4):504–14.CrossRef
27.
go back to reference Francisco N, Fang Y, Ding L, Feng S, Yang Y, Wu M, et al. Diagnostic accuracy of a selected signature gene set that discriminates active pulmonary tuberculosis and other pulmonary diseases. J Infect. 2017;75(6):499–510.CrossRef Francisco N, Fang Y, Ding L, Feng S, Yang Y, Wu M, et al. Diagnostic accuracy of a selected signature gene set that discriminates active pulmonary tuberculosis and other pulmonary diseases. J Infect. 2017;75(6):499–510.CrossRef
28.
go back to reference da Laux Costa L, Delcroix M, Dalla Costa E, Prestes I, Milano M, Francis S, et al. A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases. Tuberculosis (Edinb). 2015;95(4):421–5.CrossRef da Laux Costa L, Delcroix M, Dalla Costa E, Prestes I, Milano M, Francis S, et al. A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases. Tuberculosis (Edinb). 2015;95(4):421–5.CrossRef
Metadata
Title
Whole blood GBP5 protein levels in patients with and without active tuberculosis
Authors
Xiangyang Yao
Wei Liu
Xiaofei Li
Chenxi Deng
Tingdong Li
Zhouyue Zhong
Shuping Chen
Zhitan Ge
Xuejie Zhang
Shiyin Zhang
Yingbin Wang
Yongliang Liu
Chao Zheng
Shengxiang Ge
Ningshao Xia
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2022
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07214-8

Other articles of this Issue 1/2022

BMC Infectious Diseases 1/2022 Go to the issue