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http://dx.doi.org/10.3904/kjim.2015.407

Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response  

Nam, Sung-Jin (Department of Internal Medicine, Gyeongsang National University Changwon Hospital)
Jeong, Jee-Yeong (Department of Biochemistry, Kosin University College of Medicine)
Jang, Tae-Won (Department of Internal Medicine, Kosin University College of Medicine)
Jung, Mann-Hong (Department of Internal Medicine, Kosin University College of Medicine)
Chun, Bong-Kwon (Department of Pathology, Kosin University College of Medicine)
Cha, Hee-Jae (Department of Parasitology and Genetics, Kosin University College of Medicine)
Oak, Chul-Ho (Department of Internal Medicine, Kosin University College of Medicine)
Publication Information
The Korean journal of internal medicine / v.31, no.4, 2016 , pp. 694-702 More about this Journal
Abstract
Background/Aims: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. Methods: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. Results: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. Conclusions: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions.
Keywords
Phosphopyruvate hydratase; C-reactive protein; Diagnosis; Response; Tuberculosis, pulmonary;
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1 The Lancet Infectious Diseases. The deadly synergy of HIV and tuberculosis. Lancet Infect Dis 2010;10:441.   DOI
2 Sunnetcioglu A, Sunnetcioglu M, Binici I, Baran AI, Karahocagil MK, Saydan MR. Comparative analysis of pulmonary and extrapulmonary tuberculosis of 411 cases. Ann Clin Microbiol Antimicrob 2015;14:34.   DOI
3 Westaway MS. Useful symptom complexes in the detection of tuberculosis. S Afr Med J 1992;81:432.
4 American Thoracic Society. Diagnostic standards and classification of tuberculosis. Am Rev Respir Dis 1990;142:725-735.   DOI
5 Bua A, Molicotti P, Delogu G, et al. QuantiFERON TB Gold: a new method for latent tuberculosis infection. New Microbiol 2007;30:477-480.
6 Pai M, Joshi R, Bandyopadhyay M, et al. Sensitivity of a whole-blood interferon-gamma assay among patients with pulmonary tuberculosis and variations in T-cell responses during anti-tuberculosis treatment. Infection 2007;35:98-103.   DOI
7 Johnson JL, Geldenhuys H, Thiel BA, et al. Effect of isoniazid therapy for latent TB infection on QuantiFERON-TB gold in-tube responses in adults with positive tuberculin skin test results in a high TB incidence area: a controlled study. Chest 2014;145:612-617.   DOI
8 Kuralay F, Tokgoz Z, Comlekci A. Diagnostic usefulness of tumour marker levels in pleural effusions of malignant and benign origin. Clin Chim Acta 2000;300:43-55.   DOI
9 Li CS, Cheng BC, Ge W, Gao JF. Clinical value of CYFRA21-1, NSE, CA15-3, CA19-9 and CA125 assay in the elderly patients with pleural effusions. Int J Clin Pract 2007;61:444-448.   DOI
10 Inoue S, Takahashi H, Kaneko K. The fluctuations of neuron-specific enolase (NSE) levels of cerebrospinal fluid during bacterial meningitis: the relationship between the fluctuations of NSE levels and neurological complications or outcome. Acta Paediatr Jpn 1994;36:485-488.   DOI
11 Kang YJ, Jo JO, Ock MS, et al. Over-expression of thymosin beta4 in granulomatous lung tissue with active pulmonary tuberculosis. Tuberculosis (Edinb) 2014;94:323-331.   DOI
12 Collazos J, Esteban C, Fernandez A, Genolla J. Measurement of the serum tumor marker neuron-specific enolase in patients with benign pulmonary diseases. Am J Respir Crit Care Med 1994;150:143-145.   DOI
13 Song TJ, Choi YC, Lee KY, Kim WJ. Serum and cerebrospinal fluid neuron-specific enolase for diagnosis of tuberculous meningitis. Yonsei Med J 2012;53:1068-1072.   DOI
14 Stammet P, Collignon O, Hassager C, et al. Neuron-specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at $33^{\circ}C$ and $36^{\circ}C$. J Am Coll Cardiol 2015;65:2104-2114.   DOI
15 Choi CM, Kang CI, Jeung WK, Kim DH, Lee CH, Yim JJ. Role of the C-reactive protein for the diagnosis of TB among military personnel in South Korea. Int J Tuberc Lung Dis 2007;11:233-236.
16 Honda K, Ohga S, Takada H, et al. Neuron-specific enolase in hemophagocytic lymphohistiocytosis: a potential indicator for macrophage activation? Int J Hematol 2000;72:55-60.
17 Heitmann L, Abad Dar M, Schreiber T, et al. The IL-13/IL-4R${\alpha}$ axis is involved in tuberculosis-associated pathology. J Pathol 2014;234:338-350.   DOI
18 Lugo-Villarino G, Neyrolles O. Of clots and granulomas: platelets are new players in immunity to tuberculosis. J Infect Dis 2014;210:1687-1690.   DOI
19 Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603-662.   DOI
20 Cheng VC, Yam WC, Hung IF, et al. Clinical evaluation of the polymerase chain reaction for the rapid diagnosis of tuberculosis. J Clin Pathol 2004;57:281-285.   DOI
21 Heo EY, Chun EJ, Lee CH, et al. Radiographic improvement and its predictors in patients with pulmonary tuberculosis. Int J Infect Dis 2009;13:e371-376.   DOI
22 Kang YA, Kwon SY, Yoon HI, Lee JH, Lee CT. Role of C-reactive protein and procalcitonin in differentiation of tuberculosis from bacterial community acquired pneumonia. Korean J Intern Med 2009;24:337-342.   DOI
23 Jasmer RM, Nahid P, Hopewell PC. Clinical practice: latent tuberculosis infection. N Engl J Med 2002;347:1860-1866.   DOI
24 Koster MJ, Broekhuizen BD, Minnaard MC, et al. Diagnostic properties of C-reactive protein for detecting pneumonia in children. Respir Med 2013;107:1087-1093.   DOI
25 Bafadhel M, Clark TW, Reid C, et al. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest 2011;139:1410-1418.   DOI
26 Whalen CC. Diagnosis of latent tuberculosis infection: measure for measure. JAMA 2005;293:2785-2787.   DOI
27 Lima MM, Trindade A, Carnavalli F, Bolognesi Melchior AC, Chin CM, Dos Santos JL. Tuberculosis: challenges to improve the treatment. Curr Clin Pharmacol 2015;10:242-251.   DOI