Abstract
Introduction
Studies on biomarkers in tuberculosis are focused on pulmonary forms of this disease (PTB), and only limited information is currently available on biomarkers of extra-pulmonary tuberculosis (EPTB).
Methods
Serum samples from 24 patients with PTB, 29 patients with EPTB and 27 healthy controls were obtained, and the levels of interferon-gamma, chemokine ligand 9, mannose-binding lectin (MBL), tumor marker Ca-125 and adenosine deaminase were determined.
Results
The circulating levels of all tested biomarkers in the serum were significantly higher in PTB and EPTB patients than in controls. However, there were no significant differences in the levels of the biomarkers between patients with PTB and EPTB, with the exception of serum levels of MBL which were significantly higher in patients with EPTB than in patients with PTB (p = 0.01). In patients with EPTB, no significant differences were observed in biomarker levels among patients with or without concomitant PTB involvement. Based on MBL serum levels, ROC curve analysis showed an AUC of 0.85 for EPTB versus non-EPTB. The optimal cut-off value of MBL serum levels for EPTB versus non-EPTB was 1,000 μg/ml, with a sensitivity and specificity of 79.3 and 78.0 %, respectively.
Conclusions
Biomarkers usually present as acute phase reactants and do not enable pulmonary forms to be differentiated from more serious or extra-pulmonary forms. MBL may be an exception.
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References
Peto HM, Pratt RH, Harrington TA, LoBue PA, Armstrong LR. Epidemiology of extra-pulmonary tuberculosis in the United States, 1993–2006. Clin Infect Dis. 2009;49:1350–7.
Yang Z, Kong Y, Wilson F, Foxman B, Fowler AH, Marrs CF, et al. Identification of risk factors for extra-pulmonary tuberculosis. Clin Infect Dis. 2004;38:199–205.
Ilgazli A, Boyaci H, Basyigit I, Yildiz F. Extra-pulmonary tuberculosis: clinical and epidemiologic spectrum of 636 cases. Arch Med Res. 2004;35:435–41.
Sanz-Canalejas L, Gómez-Mampaso E, Cantón-Moreno R, Varona-Crespo C, Fortún J, Dronda F. Peliosis hepatis due to disseminated tuberculosis in a patient with AIDS. Infection. 2013;42:185–9.
Kim CH, Lim JK, Lee SY, Won DI, Cha SI, Park JY, Lee WK, Lee J. Predictive factors for tuberculosis in patients with a TB-PCR-negative bronchial aspirate. Infection. 2013;41:187–94. doi:10.1007/s15010-012-0394-7.
Jones BE, Young SM, Antoniskis D, Davidson PT, Kramer F, Barnes PF. Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. Am Rev Respir Dis. 1993;148:1292–7.
Fortún J, Martín-Dávila P, Navas E, López-Vélez R, Pintado V, Cobo J, et al. Changes in the epidemiology of tuberculosis: the influence of international migration flows. Enferm Infecc Microbiol Clin. 2011;29:654–9.
Frieden TR, Sterling TR, Munsiff SS, Watt CJ, Dye C. Tuberculosis. Lancet. 2003;362:887–99.
Ameglio F, Giannarelli D, Cordiali-Fei P, et al. Use of discriminant analys is to assess disease activity in pulmonary tuberculosis with a panel of specific and non-specific serum markers. Am J Clin Pathol. 1994;101:719–25.
Aoki Y, Katoh O, Nakanishi Y, et al. A comparison study of IFNgamma, ADA, and CA125 as the diagnostic parameters in tuberculous pleuritis. Respir Med. 1994;88:139–43.
Taha RA, Kotsimbos TC, Song YL, et al. IFN-gamma and IL-12 are increased in active compared with inactive tuberculosis. Am J Respir Crit Care Med. 1997;155:1135–9.
Verbon A, Juffermans N, Van Deventer SJ, et al. Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment. Clin Exp Immunol. 1999;115:110–3.
Cosar H, Ozkinay F, Onay H, Bayram N, Bakiler AR, Anil M, Ca D, Ozkinay C. Low levels of mannose-binding lectin confers protection against tuberculosis in Turkish children. Eur J Clin Microbiol Infect Dis. 2008;27:1165–9.
Fortún J, Martín-Davila P, Méndez R, Martínez A, Norman F, Rubi J, et al. Ca-125: a useful marker to distinguish pulmonary tuberculosis from other pulmonary infections. Open Respir Med J. 2009;3:123–7.
Capparelli R, Iannaccone M, Palumbo D, Medaglia C, Moscariello E, Russo A, Iannelli D. Role played by human mannose-binding lectin polymorphisms in pulmonary tuberculosis. J Infect Dis. 2009;199:666–72.
Hasan Z, Jamil B, Khan J, Ali R, Khan MA, Nasir N, Yusuf MS, Jamil S, Irfan M, Hussain R. 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;69:259–67.
Huang WC, Tseng CW, Chang KM, Hsu JY, Chen JH, Shen GH. Usefulness of tumor marker CA-125 serum levels for the follow-up of therapeutic responses in tuberculosis patients with and without serositis. Jpn J Infect Dis. 2011;64:367–72.
Yilmaz A, Ece F, Bayramgürler B, Akkaya E, Baran R. The value of Ca 125 in the evaluation of tuberculosis activity. Respir Med. 2001;95:666–9.
Ad-hoc Committee of the Scientific Assembly on Microbiology, Tuberculosis, and Pulmonary Infections. Diagnostic standards and classification of tuberculosis in adults and children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med 2000;161:1376–95.
Denholm JT, McBryde ES, Eisen DP. Mannose-binding lectin and susceptibility to tuberculosis: a meta-analysis. Clin Exp Immunol. 2010;162:84–90.
Huang WC, Tseng CW, Chang KM, Hsu JY, Chen JH, Shen GH. Usefulness of tumor marker CA-125 serum levels for the follow-up of therapeutic responses in tuberculosis patients with and without serositis. Jpn J Infect Dis. 2011;64:367–72.
Yilmaz A, Ece F, Bayramgürler B, Akkaya E, Baran RB. The value of Ca 125 in the evaluation of tuberculosis activity. Respir Med. 2001;95:666–9.
Candocia SA, Locker GY. Elevated serum CA 125 secondary to tuberculous peritonitis. Cancer. 1993;72(6):2016–8.
Simsek H, Savas MC, Kadayifci A, et al. Elevated serum CA 125 concentration in patients with tuberculous peritonitis: a case-control study. Am J Gastroenterol. 1997;92:1174–6.
Younossian AB, Rochat T, Favre L, Janssens JP. Ascites and highly elevated CA-125 levels in a case of peritoneal tuberculosis. Scand J Infect Dis. 2006;38:216–8.
Acknowledgments
We thank Thomas O’Boyle for his assistance with the manuscript. This collaboration was supported by the Department of Infectious Diseases of Ramon y Cajal Hospital of Madrid, Spain.
Financial statement
There was no specific financial support for this study. Parts of this dataset were generated as during routine work at the Hospital Ramon y Cajal of Madrid, Spain.
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Fortún, J., Martín-Dávila, P., Gómez-Mampaso, E. et al. Extra-pulmonary tuberculosis: a biomarker analysis. Infection 42, 649–654 (2014). https://doi.org/10.1007/s15010-014-0602-8
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DOI: https://doi.org/10.1007/s15010-014-0602-8