Kinetics of T-cell-based assays on cerebrospinal fluid and peripheral blood mononuclear cells in patients with tuberculous meningitis.
OBJECTIVE
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 (≥ 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-γ)-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-γ-producing T-cells in CSF-MC during the early phase of anti-TB therapy may be predictive of clinical failure.
Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea.
Ki-Ho
KH
Park
Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea.
Mi Suk
MS
Lee
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sang-Oh
SO
Lee
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sang-Ho
SH
Choi
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Yang Soo
YS
Kim
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Jun Hee
JH
Woo
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Joong Koo
JK
Kang
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sang-Ahm
SA
Lee
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sung-Han
SH
Kim
D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000134:cerebrospinal fluid; D059425:Interferon-gamma Release Tests; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D056910:Republic of Korea; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology
D000995:Antitubercular Agents; D015415:Biomarkers; C573415:IFNG protein, human; D007371:Interferon-gamma
Cerebrospinal fluid; Enzyme-linked immunosorbent assay; Meningitis; Tuberculosis