IP-10, MCP-1, MCP-2, MCP-3, and IL-1RA hold promise as biomarkers for infection with M. tuberculosis in a whole blood based T-cell assay

被引:103
作者
Ruhwald M. [1 ,2 ]
Bjerregaard-Andersen M. [3 ,4 ]
Rabna P. [4 ]
Eugen-Olsen J. [2 ]
Ravn P. [2 ,5 ]
机构
[1] Dep. of Infectious Diseases 144, Copenhagen University, Hvidovre Hospital
[2] Clinical Research Centre 136, Copenhagen University, Hvidovre Hospital
[3] Dep. of Infectious Diseases Q, Skejby University Hospital
[4] Bandim Health Project, 1004 Bissau Codex
[5] Department of Medicine, Copenhagen University, Herlev Hospital
关键词
Tuberculosis; Tuberculin Skin Test; Diagnostic Potential; Interferon Gamma Release Assay; Sputum Smear Microscopy;
D O I
10.1186/1756-0500-2-19
中图分类号
学科分类号
摘要
Background. IFN- responses to M. tuberculosis antigens are used as in-vitro diagnostic tests for tuberculosis infection. The tests are highly specific but sensitivity may be impaired due to immuno-suppression. The objective of this small exploratory study was to compare three novel biomarkers for in-vitro diagnosis of tuberculosis - MCP-1, MCP-3 and IL-1RA - with the current established biomarker IFN- and the newly described IP-10 and MCP-2. Methods. Whole blood from 8 patents with active tuberculosis and from 7 healthy controls was stimulated with M. tuberculosis specific antigens and mitogen in the Quantiferon In Tube test tubes. Levels of biomarkers were measured using Luminex and ELISA (IFN-). Results. We found all five new biomarkers were expressed in significantly higher concentrations compared to IFN-. IP-10 and MCP-3 levels in the un-stimulated samples were higher in patients compared with controls. Conclusion. All biomarkers had diagnostic potential as they could differentiate between the patients and the controls. IP-10 and MCP-2 seemed most promising as they were expressed in high levels with antigen stimulation and were low in the un-stimulated samples. Further studies are needed to explore the potential of these highly expressed novel biomarkers individually and in combination. © 2009 Ruhwald et al.
引用
收藏
相关论文
共 21 条
[11]  
Ruhwald M., Bodmer T., Maier C., Jepsen M., Andersen M.B., Eugen-Olsen J., Et al., Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of TB, Eur Respir J, 32, 6, pp. 1607-1615, (2008)
[12]  
Proost P., Wuyts A., Van Damme J., Human monocyte chemotactic proteins-2 and -3: Structural and functional comparison with MCP-1, J Leukoc Biol, 59, pp. 67-74, (1996)
[13]  
Ragno S., Romano M., Howell S., Pappin D.J., Jenner P.J., Colston M.J., Changes in gene expression in macrophages infected with Mycobacterium tuberculosis: A combined transcriptomic and proteomic approach, Immunology, 104, pp. 99-108, (2001)
[14]  
Lee J.H., Chang J.H., Changes of plasma interleukin-1 receptor antagonist, interleukin-8 and other serologic markers during chemotherapy in patients with active pulmonary tuberculosis, Korean J Intern Med, 18, pp. 138-145, (2003)
[15]  
Daly C., Rollins B.J., Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: Therapeutic opportunities and controversies, Microcirculation, 10, pp. 247-257, (2003)
[16]  
Lee J.S., Song C.H., Lim J.H., Lee K.S., Kim H.J., Park J.K., Et al., Monocyte chemotactic protein-1 production in patients with active pulmonary tuberculosis and tuberculous pleurisy, Inflamm Res, 52, pp. 297-304, (2003)
[17]  
Juffermans N.P., Verbon A., Van Deventer S.J., Van D.H., Belisle J.T., Ellis M.E., Et al., Elevated chemokine concentrations in sera of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients with tuberculosis: A possible role for mycobacterial lipoarabinomannan, Infect Immun, 67, pp. 4295-4297, (1999)
[18]  
Miotto D., Christodoulopoulos P., Olivenstein R., Taha R., Cameron L., Tsicopoulos A., Et al., Expression of IFN-gamma-inducible protein
[19]  
Monocyte chemotactic proteins 1, 3, and 4
[20]  
And eotaxin in TH1- and TH2-mediated lung diseases, J Allergy Clin Immunol, 107, pp. 664-670, (2001)