Kinetics of T-cell-based assays on cerebrospinal fluid and peripheral blood mononuclear cells in patients with tuberculous meningitis
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Background/Aims: The goal of this study was to monitor tuberculosis (TB)-specificT-cell responses in cerebrospinal f luid-mononuclear cells (CSF-MCs) andperipheral blood mononuclear cells (PBMCs) in patients with tuberculous meningitis(TBM) over the course of anti-TB therapy. Methods: Adult patients (≥ 16 years) with TBM admitted to Asan Medical Center,Seoul, South Korea, were prospectively enrolled between April 2008 and April2011. Serial blood or CSF samples were collected over the course of the anti-TBtherapy, and analyzed using an enzyme-linked immunosorbent spot (ELISPOT)assay. Results: Serial ELISPOT assays were performed on PBMCs from 17 patients (sevendefinite, four probable, and six possible TBM) and CSF-MC from nine patients(all definite TBM). The median number of interferon-gamma (IFN-γ)-producingT-cells steadily increased during the first 6 months after commencement ofanti-TB therapy in PBMCs. Serial CSF-MC ELISPOT assays revealed significantvariability in immune responses during the first 6 weeks of anti-TB therapy,though early increases in CSF-MC ELISPOT results were associated with treatmentfailure or paradoxical response. Conclusions: Serial analysis of PBMCs by ELISPOT during the course of treatmentwas ineffective for predicting clinical response. However, increases inTB-specific IFN-γ-producing T-cells in CSF-MC during the early phase of anti-TB therapy may be predictive of clinical failure.
Abstract
Background/Aims: The goal of this study was to monitor tuberculosis (TB)-specificT-cell responses in cerebrospinal f luid-mononuclear cells (CSF-MCs) andperipheral blood mononuclear cells (PBMCs) in patients with tuberculous meningitis(TBM) over the course of anti-TB therapy. Methods: Adult patients (≥ 16 years) with TBM admitted to Asan Medical Center,Seoul, South Korea, were prospectively enrolled between April 2008 and April2011. Serial blood or CSF samples were collected over the course of the anti-TBtherapy, and analyzed using an enzyme-linked immunosorbent spot (ELISPOT)assay. Results: Serial ELISPOT assays were performed on PBMCs from 17 patients (sevendefinite, four probable, and six possible TBM) and CSF-MC from nine patients(all definite TBM). The median number of interferon-gamma (IFN-γ)-producingT-cells steadily increased during the first 6 months after commencement ofanti-TB therapy in PBMCs. Serial CSF-MC ELISPOT assays revealed significantvariability in immune responses during the first 6 weeks of anti-TB therapy,though early increases in CSF-MC ELISPOT results were associated with treatmentfailure or paradoxical response. Conclusions: Serial analysis of PBMCs by ELISPOT during the course of treatmentwas ineffective for predicting clinical response. However, increases inTB-specific IFN-γ-producing T-cells in CSF-MC during the early phase of anti-TB therapy may be predictive of clinical failure.
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