The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Kinetics of T-cell-based assays on cerebrospinal fluid and peripheral blood mononuclear cells in patients with tuberculous meningitis

  • Park, Ki-Ho (Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University School of Medicine) ;
  • Lee, Mi Suk (Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University School of Medicine) ;
  • Lee, Sang-Oh (Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Choi, Sang-Ho (Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Yang Soo (Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Woo, Jun Hee (Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kang, Joong Koo (Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Sang-Ahm (Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Sung-Han (Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2013.11.04
  • Accepted : 2013.12.19
  • Published : 2014.11.01
⟨ Previous Next ⟩

Abstract

Background/Aims: The goal of this study was to monitor tuberculosis (TB)-specific T-cell responses in cerebrospinal f luid-mononuclear cells (CSF-MCs) and peripheral blood mononuclear cells (PBMCs) in patients with tuberculous meningitis (TBM) over the course of anti-TB therapy. Methods: Adult patients (${\geq}16$ years) with TBM admitted to Asan Medical Center, Seoul, South Korea, were prospectively enrolled between April 2008 and April 2011. Serial blood or CSF samples were collected over the course of the anti-TB therapy, and analyzed using an enzyme-linked immunosorbent spot (ELISPOT) assay. Results: Serial ELISPOT assays were performed on PBMCs from 17 patients (seven definite, four probable, and six possible TBM) and CSF-MC from nine patients (all definite TBM). The median number of interferon-gamma (IFN-${\gamma}$)-producing T-cells steadily increased during the first 6 months after commencement of anti-TB therapy in PBMCs. Serial CSF-MC ELISPOT assays revealed significant variability in immune responses during the first 6 weeks of anti-TB therapy, though early increases in CSF-MC ELISPOT results were associated with treatment failure or paradoxical response. Conclusions: Serial analysis of PBMCs by ELISPOT during the course of treatment was ineffective for predicting clinical response. However, increases in TB-specific IFN-${\gamma}$-producing T-cells in CSF-MC during the early phase of anti-TB therapy may be predictive of clinical failure.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Kim SH, Cho OH, Park SJ, et al. Rapid diagnosis of tuberculous meningitis by T cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells. Clin Infect Dis 2010;50:1349-1358. https://doi.org/10.1086/652142
  2. Patel VB, Singh R, Connolly C, et al. Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis- endemic population. Am J Respir Crit Care Med 2010;182:569-577. https://doi.org/10.1164/rccm.200912-1931OC
  3. Kim SH, Chu K, Choi SJ, et al. Diagnosis of central nervous system tuberculosis by T-cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells. Clin Vaccine Immunol 2008;15:1356-1362. https://doi.org/10.1128/CVI.00040-08
  4. Thomas MM, Hinks TS, Raghuraman S, et al. Rapid diagnosis of Mycobacterium tuberculosis meningitis by enumeration of cerebrospinal fluid antigen-specific T-cells. Int J Tuberc Lung Dis 2008;12:651-657.
  5. Carrara S, Vincenti D, Petrosillo N, Amicosante M, Girardi E, Goletti D. Use of a T cell-based assay for monitoring efficacy of antituberculosis therapy. Clin Infect Dis 2004;38:754-756. https://doi.org/10.1086/381754
  6. Aiken AM, Hill PC, Fox A, et al. Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases. BMC Infect Dis 2006;6:66. https://doi.org/10.1186/1471-2334-6-66
  7. Kobashi Y, Mouri K, Yagi S, Obase Y, Miyashita N, Oka M. Transitional changes in T-cell responses to Mycobacterium tuberculosis-specific antigens during treatment. J Infect 2009;58:197-204. https://doi.org/10.1016/j.jinf.2008.08.009
  8. Katiyar SK, Sampath A, Bihari S, Mamtani M, Kulkarni H. Use of the QuantiFERON-TB Gold In-Tube test to monitor treatment efficacy in active pulmonary tuberculosis. Int J Tuberc Lung Dis 2008;12:1146-1152.
  9. Dheda K, Pooran A, Pai M, et al. Interpretation of Mycobacterium tuberculosis antigen-specific IFN-gamma release assays (T-SPOT.TB) and factors that may modulate test results. J Infect 2007;55:169-173. https://doi.org/10.1016/j.jinf.2007.02.005
  10. Marais S, Thwaites G, Schoeman JF, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis 2010;10:803-812. https://doi.org/10.1016/S1473-3099(10)70138-9
  11. 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. https://doi.org/10.1164/rccm.167.4.603
  12. Kim SH, Choi SJ, Kim HB, Kim NJ, Oh MD, Choe KW. Diagnostic usefulness of a T-cell based assay for extrapulmonary tuberculosis. Arch Intern Med 2007;167:2255-2259. https://doi.org/10.1001/archinte.167.20.2255
  13. Park KH, Cho OH, Ko GB, et al. Serial testing of T-SPOT. TB assays with anti-tuberculosis therapy in patients with extrapulmonay tuberculosis. Infect Chemother 2011;43:245-250. https://doi.org/10.3947/ic.2011.43.3.245
  14. Vekemans J, Lienhardt C, Sillah JS, et al. Tuberculosis contacts but not patients have higher gamma interferon responses to ESAT-6 than do community controls in The Gambia. Infect Immun 2001;69:6554-6557. https://doi.org/10.1128/IAI.69.10.6554-6557.2001
  15. Ulrichs T, Anding R, Kaufmann SH, Munk ME. Numbers of IFN-gamma-producing cells against ESAT-6 increase in tuberculosis patients during chemotherapy. Int J Tuberc Lung Dis 2000;4:1181-1183.
  16. Ferrand RA, Bothamley GH, Whelan A, Dockrell HM. Interferon-gamma responses to ESAT-6 in tuberculosis patients early into and after anti-tuberculosis treatment. Int J Tuberc Lung Dis 2005;9:1034-1039.
  17. Al-Attiyah R, Mustafa AS, Abal AT, Madi NM, Andersen P. Restoration of mycobacterial antigen-induced proliferation and interferon-gamma responses in peripheral blood mononuclear cells of tuberculosis patients upon effective chemotherapy. FEMS Immunol Med Microbiol 2003;38:249-256. https://doi.org/10.1016/S0928-8244(03)00166-4
  18. Pathan AA, Wilkinson KA, Klenerman P, et al. Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. J Immunol 2001;167:5217-5225. https://doi.org/10.4049/jimmunol.167.9.5217
  19. Lee SW, Lee CT, Yim JJ. Serial interferon-gamma release assays during treatment of active tuberculosis in young adults. BMC Infect Dis 2010;10:300. https://doi.org/10.1186/1471-2334-10-300
  20. Chee CB, KhinMar KW, Gan SH, et al. Tuberculosis treatment effect on T-cell interferon-gamma responses to Mycobacterium tuberculosis-specific antigens. Eur Respir J 2010;36:355-361. https://doi.org/10.1183/09031936.00151309
  21. Cheng VC, Yam WC, Woo PC, et al. Risk factors for development of paradoxical response during antituberculosis therapy in HIV-negative patients. Eur J Clin Microbiol Infect Dis 2003;22:597-602. https://doi.org/10.1007/s10096-003-0998-z
  22. Kim SH, Kim YS. Immunologic paradox in the diagnosis of tuberculous meningitis. Clin Vaccine Immunol 2009;16:1847-1849. https://doi.org/10.1128/CVI.00321-09
  23. Thwaites GE, Chau TT, Stepniewska K, et al. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. Lancet 2002;360:1287-1292. https://doi.org/10.1016/S0140-6736(02)11318-3
  24. Thwaites GE, Nguyen DB, Nguyen HD, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med 2004;351:1741-1751. https://doi.org/10.1056/NEJMoa040573

Cited by

  1. Diagnostic Usefulness of IFN-Gamma Releasing Assays Compared With Conventional Tests in Patients With Disseminated Tuberculosis vol.94, pp.28, 2014, https://doi.org/10.1097/md.0000000000001094
  2. Benefit of ELISpot in early diagnosis of tuberculous meningoencephalitis: Case report and literature review vol.1, pp.3, 2014, https://doi.org/10.1016/j.ensci.2015.10.004
  3. Infectious immunity in the central nervous system and brain function vol.18, pp.2, 2017, https://doi.org/10.1038/ni.3656