Diagnostic value of plasma CXC chemokine ligand 9 in tuberculosis: a systematic review and meta-analysis_West China Medical Journal

Authors：

LIU Hai , WANG Haojun ^共 , HE Yuyu , MENG Qing , WU Changxin , YANG Caiting ,  DONG Li

Institutes of Biomedical Sciences, Shanxi University, Taiyuan, Shanxi 030006, P. R. China;

Corresponding author：

DONG Li, Email: Dongli@sxu.edu.cn

Keywords：

Active tuberculosis; latent infection; CXC chemokine ligand 9; diagnosis; meta-analysis

DOI：

10.7507/1002-0179.202305017

Video：

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Objective To systematically evaluate the value of CXC chemokine ligand 9 (CXCL9) in the diagnosis of tuberculosis. Methods Literature on the diagnosis of tuberculosis by plasma CXCL9 were collected by searching PubMed, EBSCO, China National Knowledge Infrastructure and Wanfang databases form establishment to September 2022, and then literature screening, data extraction and quality assessment were performed independently by two researchers. Meta-analysis was performed using Review Manager 5.3 and Stata 15 softwares. Results According to the inclusion and exclusion criteria, 10 articles were selected, including 1586 participants from 5 countries and regions. Meta-analysis results showed that the positive rate of CXCL9 was higher in active tuberculosis patients than that in healthy people and latent tuberculosis patients [active tuberculosis patients vs. healthy people: odds ratio (OR)=21.69, 95% confidence interval (CI) (6.52, 72.16), P<0.00001; active tuberculosis patients vs. latent tuberculosis patients: OR=10.12, 95%CI (3.83, 26.76), P<0.00001]. The sensitivity and specificity of plasma CXCL9 in distinguishing active tuberculosis patients from healthy people were 0.84 [95%CI (0.77, 0.90)] and 0.82 [95%CI (0.63, 0.92)], respectively; the sensitivity and specificity of plasma CXCL9 in distinguishing active tuberculosis patients from latent tuberculosis patients were 0.77 [95%CI (0.56, 0.90)] and 0.72 [95%CI (0.40, 0.91)], respectively. Subgroup analysis showed that the infection status of human immunodeficiency virus had some impact on heterogeneity, while other factors had limited impact on heterogeneity. Egger test showed that there was no publication bias (active tuberculosis patients vs. healthy people: P=0.976; active tuberculosis patients vs. latent tuberculosis patients: P=0.606). Conclusion CXCL9 has a high diagnostic value for tuberculosis patients and may be used as a new biomarker to diagnose tuberculosis.

Citation： LIU Hai, WANG Haojun, HE Yuyu, MENG Qing, WU Changxin, YANG Caiting, DONG Li. Diagnostic value of plasma CXC chemokine ligand 9 in tuberculosis: a systematic review and meta-analysis. West China Medical Journal, 2023, 38(11): 1719-1725. doi: 10.7507/1002-0179.202305017 Copy

1.	Adigun R, Singh R. Tuberculosis//StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2022.
2.	World Health Organization. Global tuberculosis report 2021. Geneva: World Health Organization, 2021.
3.	House IG, Savas P, Lai J, et al. Macrophage-derived CXCL9 and CXCL10 are required for antitumor immune responses following immune checkpoint blockade. Clin Cancer Res, 2020, 26(2): 487-504.
4.	Marcovecchio PM, Thomas G, Salek-Ardakani S. CXCL9-expressing tumor-associated macrophages: new players in the fight against cancer. J Immunother Cancer, 2021, 9(2): e002045.
5.	Neo SY, Lundqvist A. The multifaceted roles of CXCL9 within the tumor microenvironment. Adv Exp Med Biol, 2020, 1231: 45-51.
6.	Sivro A, McKinnon LR, Yende-Zuma N, et al. Plasma cytokine predictors of tuberculosis recurrence in antiretroviral-treated human immunodeficiency virus-infected individuals from Durban, South Africa. Clin Infect Dis, 2017, 65(5): 819-826.
7.	Korma W, Mihret A, Chang Y, et al. Antigen-specific cytokine and chemokine gene expression for diagnosing latent and active tuberculosis. Diagnostics (Basel), 2020, 10(9): 716.
8.	Yang Q, Cai Y, Zhao W, et al. IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after antituberculosis treatment. Clin Vaccine Immunol, 2014, 21(12): 1635-1644.
9.	La Manna MP, Orlando V, Li Donni P, et al. Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease. PLoS One, 2018, 13(3): e0192664.
10.	Shang X, Wang L, Liu Y, et al. Diagnostic value of CXCR3 and its ligands in spinal tuberculosis. Exp Ther Med, 2021, 21(1): 73.
11.	Kumar NP, Moideen K, Nancy A, et al. Plasma chemokines are biomarkers of disease severity, higher bacterial burden and delayed sputum culture conversion in pulmonary tuberculosis. Sci Rep, 2019, 9(1): 18217.
12.	Farr K, Ravindran R, Strnad L, et al. Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV. PLoS One, 2018, 13(10): e0206119.
13.	谢舒枝, 盛星, 陈骑, 等. 趋化因子 CXCL9 在结核病患者血浆中的表达及临床意义. 新发传染病电子杂志, 2017, 2(2): 93-95.
14.	Jacobs R, Malherbe S, Loxton AG, et al. Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response. Oncotarget, 2016, 7(36): 57581-57592.
15.	方木通, 杨倩婷, 邓群益, 等. CXCL9 在结核患者中的表达及其在结核病诊断中的应用. 广东医学, 2015, 36(23): 3676-3678.
16.	Lee K, Chung W, Jung Y, et al. CXCR3 ligands as clinical markers for pulmonary tuberculosis. Int J Tuberc Lung Dis, 2015, 19(2): 191-199.
17.	Chung WY, Lee KS, Jung YJ, et al. A TB antigen-stimulated CXCR3 ligand assay for the diagnosis of active pulmonary TB. Chest, 2014, 146(2): 283-291.
18.	Cai L, Li Z, Guan X, et al. The research progress of host genes and tuberculosis susceptibility. Oxid Med Cell Longev, 2019, 2019: 9273056.
19.	Sun H, Fan J, Shang X, et al. Study on the relationship between CXCR3 and its ligands and tubal tuberculosis. Life Sci, 2021, 272: 119047.
20.	Aranday-Cortes E, Bull NC, Villarreal-Ramos B, et al. Upregulation of IL-17A, CXCL9 and CXCL10 in early-stage granulomas induced by Mycobacterium bovis in cattle. Transbound Emerg Dis, 2013, 60(6): 525-537.
21.	Hasan Z, Jamil B, Khan J, et al. Relationship between circulating levels of IFN-gamma, IL-10, CXCL9 and CCL2 in pulmonary and extrapulmonary tuberculosis is dependent on disease severity. Scand J Immunol, 2009, 69(3): 259-267.
22.	Li Y, He D, Che Y, et al. Monokine induced by gamma interferon for detecting pulmonary tuberculosis: a diagnostic meta-analysis. Medicine (Baltimore), 2020, 99(47): e23302.
23.	Zhang M, Li D, Hu ZD, et al. The diagnostic utility of pleural markers for tuberculosis pleural effusion. Ann Transl Med, 2020, 8(9): 607.
24.	López-Ramos JE, Macías-Segura N, Cuevas-Cordoba B, et al. Improvement in the diagnosis of tuberculosis combining Mycobacterium tuberculosis immunodominant peptides and serum host biomarkers. Arch Med Res, 2018, 49(3): 147-153.
25.	Palmer MV, Thacker TC, Rabideau MM, et al. Biomarkers of cell-mediated immunity to bovine tuberculosis. Vet Immunol Immunopathol, 2020, 220: 109988.
26.	Bai X, Chmura K, Ovrutsky AR, et al. Mycobacterium tuberculosis increases IP-10 and MIG protein despite inhibition of IP-10 and MIG transcription. Tuberculosis (Edinb), 2011, 91(1): 26-35.
27.	DiNardo AR, Rajapakshe K, Nishiguchi T, et al. DNA hypermethylation during tuberculosis dampens host immune responsiveness. J Clin Invest, 2020, 130(6): 3113-3123.
28.	Forrellad MA, Klepp LI, Gioffré A, et al. Virulence factors of the Mycobacterium tuberculosis complex. Virulence, 2013, 4(1): 3-66.
29.	Wang L, Tian XD, Yu Y, et al. Evaluation of the performance of two tuberculosis interferon gamma release assays (IGRA-ELISA and T-SPOT. TB) for diagnosing Mycobacterium tuberculosis infection. Clin Chim Acta, 2018, 479: 74-78.
30.	Boff D, Crijns H, Janssens R, et al. The chemokine fragment CXCL9(74-103) diminishes neutrophil recruitment and joint inflammation in antigen-induced arthritis. J Leukoc Biol, 2018, 104(2): 413-422.
31.	Razis E, Kalogeras KT, Kotsantis I, et al. The role of CXCL13 and CXCL9 in early breast cancer. Clin Breast Cancer, 2020, 20(1): e36-e53.
32.	La Manna MP, Tamburini B, Orlando V, et al. LIODetect^®TB-ST: evaluation of novel blood test for a rapid diagnosis of active pulmonary and extra-pulmonary tuberculosis in IGRA confirmed patients. Tuberculosis (Edinb), 2021, 130: 102119.

1. Adigun R, Singh R. Tuberculosis//StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2022.
2. World Health Organization. Global tuberculosis report 2021. Geneva: World Health Organization, 2021.
3. House IG, Savas P, Lai J, et al. Macrophage-derived CXCL9 and CXCL10 are required for antitumor immune responses following immune checkpoint blockade. Clin Cancer Res, 2020, 26(2): 487-504.
4. Marcovecchio PM, Thomas G, Salek-Ardakani S. CXCL9-expressing tumor-associated macrophages: new players in the fight against cancer. J Immunother Cancer, 2021, 9(2): e002045.
5. Neo SY, Lundqvist A. The multifaceted roles of CXCL9 within the tumor microenvironment. Adv Exp Med Biol, 2020, 1231: 45-51.
6. Sivro A, McKinnon LR, Yende-Zuma N, et al. Plasma cytokine predictors of tuberculosis recurrence in antiretroviral-treated human immunodeficiency virus-infected individuals from Durban, South Africa. Clin Infect Dis, 2017, 65(5): 819-826.
7. Korma W, Mihret A, Chang Y, et al. Antigen-specific cytokine and chemokine gene expression for diagnosing latent and active tuberculosis. Diagnostics (Basel), 2020, 10(9): 716.
8. Yang Q, Cai Y, Zhao W, et al. IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after antituberculosis treatment. Clin Vaccine Immunol, 2014, 21(12): 1635-1644.
9. La Manna MP, Orlando V, Li Donni P, et al. Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease. PLoS One, 2018, 13(3): e0192664.
10. Shang X, Wang L, Liu Y, et al. Diagnostic value of CXCR3 and its ligands in spinal tuberculosis. Exp Ther Med, 2021, 21(1): 73.
11. Kumar NP, Moideen K, Nancy A, et al. Plasma chemokines are biomarkers of disease severity, higher bacterial burden and delayed sputum culture conversion in pulmonary tuberculosis. Sci Rep, 2019, 9(1): 18217.
12. Farr K, Ravindran R, Strnad L, et al. Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV. PLoS One, 2018, 13(10): e0206119.
13. 谢舒枝, 盛星, 陈骑, 等. 趋化因子 CXCL9 在结核病患者血浆中的表达及临床意义. 新发传染病电子杂志, 2017, 2(2): 93-95.
14. Jacobs R, Malherbe S, Loxton AG, et al. Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response. Oncotarget, 2016, 7(36): 57581-57592.
15. 方木通, 杨倩婷, 邓群益, 等. CXCL9 在结核患者中的表达及其在结核病诊断中的应用. 广东医学, 2015, 36(23): 3676-3678.
16. Lee K, Chung W, Jung Y, et al. CXCR3 ligands as clinical markers for pulmonary tuberculosis. Int J Tuberc Lung Dis, 2015, 19(2): 191-199.
17. Chung WY, Lee KS, Jung YJ, et al. A TB antigen-stimulated CXCR3 ligand assay for the diagnosis of active pulmonary TB. Chest, 2014, 146(2): 283-291.
18. Cai L, Li Z, Guan X, et al. The research progress of host genes and tuberculosis susceptibility. Oxid Med Cell Longev, 2019, 2019: 9273056.
19. Sun H, Fan J, Shang X, et al. Study on the relationship between CXCR3 and its ligands and tubal tuberculosis. Life Sci, 2021, 272: 119047.
20. Aranday-Cortes E, Bull NC, Villarreal-Ramos B, et al. Upregulation of IL-17A, CXCL9 and CXCL10 in early-stage granulomas induced by Mycobacterium bovis in cattle. Transbound Emerg Dis, 2013, 60(6): 525-537.
21. Hasan Z, Jamil B, Khan J, et al. Relationship between circulating levels of IFN-gamma, IL-10, CXCL9 and CCL2 in pulmonary and extrapulmonary tuberculosis is dependent on disease severity. Scand J Immunol, 2009, 69(3): 259-267.
22. Li Y, He D, Che Y, et al. Monokine induced by gamma interferon for detecting pulmonary tuberculosis: a diagnostic meta-analysis. Medicine (Baltimore), 2020, 99(47): e23302.
23. Zhang M, Li D, Hu ZD, et al. The diagnostic utility of pleural markers for tuberculosis pleural effusion. Ann Transl Med, 2020, 8(9): 607.
24. López-Ramos JE, Macías-Segura N, Cuevas-Cordoba B, et al. Improvement in the diagnosis of tuberculosis combining Mycobacterium tuberculosis immunodominant peptides and serum host biomarkers. Arch Med Res, 2018, 49(3): 147-153.
25. Palmer MV, Thacker TC, Rabideau MM, et al. Biomarkers of cell-mediated immunity to bovine tuberculosis. Vet Immunol Immunopathol, 2020, 220: 109988.
26. Bai X, Chmura K, Ovrutsky AR, et al. Mycobacterium tuberculosis increases IP-10 and MIG protein despite inhibition of IP-10 and MIG transcription. Tuberculosis (Edinb), 2011, 91(1): 26-35.
27. DiNardo AR, Rajapakshe K, Nishiguchi T, et al. DNA hypermethylation during tuberculosis dampens host immune responsiveness. J Clin Invest, 2020, 130(6): 3113-3123.
28. Forrellad MA, Klepp LI, Gioffré A, et al. Virulence factors of the Mycobacterium tuberculosis complex. Virulence, 2013, 4(1): 3-66.
29. Wang L, Tian XD, Yu Y, et al. Evaluation of the performance of two tuberculosis interferon gamma release assays (IGRA-ELISA and T-SPOT. TB) for diagnosing Mycobacterium tuberculosis infection. Clin Chim Acta, 2018, 479: 74-78.
30. Boff D, Crijns H, Janssens R, et al. The chemokine fragment CXCL9(74-103) diminishes neutrophil recruitment and joint inflammation in antigen-induced arthritis. J Leukoc Biol, 2018, 104(2): 413-422.
31. Razis E, Kalogeras KT, Kotsantis I, et al. The role of CXCL13 and CXCL9 in early breast cancer. Clin Breast Cancer, 2020, 20(1): e36-e53.
32. La Manna MP, Tamburini B, Orlando V, et al. LIODetect^®TB-ST: evaluation of novel blood test for a rapid diagnosis of active pulmonary and extra-pulmonary tuberculosis in IGRA confirmed patients. Tuberculosis (Edinb), 2021, 130: 102119.

West China Medical Journal

Diagnostic value of plasma CXC chemokine ligand 9 in tuberculosis: a systematic review and meta-analysis

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