Korean J Intern Med.  2014 Nov;29(6):793-799. 10.3904/kjim.2014.29.6.793.

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

• Park KH
• Lee MS
• Lee SO
• Choi SH
• Kim YS
• Woo JH
• Kang JK
• Lee SA
• Kim SH

• KMID: 2070137
• DOI: http://doi.org/10.3904/kjim.2014.29.6.793

Abstract

BACKGROUND/AIMS
The goal of this study was to monitor tuberculosis (TB)-specific T-cell responses in cerebrospinal fluid-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 (> or = 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.

Keyword

Tuberculosis; Meningitis; Enzyme-linked immunosorbent assay; Cerebrospinal fluid

MeSH Terms

Adult
Antitubercular Agents/therapeutic use
Biological Markers/blood/cerebrospinal fluid
*Enzyme-Linked Immunospot Assay
Female
Humans
Interferon-gamma/blood/cerebrospinal fluid
*Interferon-gamma Release Tests
Kinetics
Male
Middle Aged
Predictive Value of Tests
Prospective Studies
Republic of Korea
T-Lymphocytes/drug effects/*immunology/metabolism/microbiology
Treatment Outcome
Tuberculosis, Meningeal/blood/cerebrospinal fluid/*diagnosis/drug therapy/immunology/microbiology
Antitubercular Agents
Biological Markers
Interferon-gamma