Abstract
Tuberculous meningitis (TBM) is the most devastating form of tuberculosis. Both intracerebral and peripheral blood immune responses may be relevant to pathogenesis, diagnosis, and outcome. In this study, the relationship between pretreatment host response, disease phenotype, and outcome in Vietnamese adults with TBM was examined. Before treatment, peripheral blood IFN-γ ELISPOT responses to the Mycobacterium tuberculosis Ags ESAT-6, CFP-10, and purified protein derivative (PPD) were a poor diagnostic predictor of TBM. Cerebrospinal fluid IL-6 concentrations at presentation were independently associated with severe disease presentation, suggesting an immunological correlate of neurological damage before treatment. Surprisingly however, elevated cerebrospinal fluid inflammatory cytokines were not associated with death or disability in HIV-negative TBM patients at presentation. HIV coinfection attenuated multiple cerebrospinal fluid inflammatory indices. Low cerebrospinal fluid IFN-γ concentrations were independently associated with death in HIV-positive TBM patients, implying that IFN-γ contributes to immunity and survival. Collectively, these results reveal the effect of HIV coinfection on the pathogenesis of TBM and suggest that intracerebral immune responses, at least in HIV-negative cases, may not be as intimately associated with disease outcome as previously thought.
| Original language | English |
|---|---|
| Pages (from-to) | 2007-2014 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 176 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1 Feb 2006 |
Cite this
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Pretreatment intracerebral and peripheral blood immune responses in vietnamese adults with tuberculous meningitis : Diagnostic value and relationship to disease severity and outcome. / Simmons, Cameron P.; Thwaites, Guy E.; Quyen, Nguyen Than Ha; Torok, Estee; Hoang, Dang Minh; Chau, Tran Thi Hong; Mai, Pham Phuong; Lan, Nguyen Thi Ngoc; Dung, Nguyen Huy; Quy, Hoang Thi; Bang, Nguyen Duc; Hien, Tran Tinh; Farrar, Jeremy.
In: Journal of Immunology, Vol. 176, No. 3, 01.02.2006, p. 2007-2014.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Pretreatment intracerebral and peripheral blood immune responses in vietnamese adults with tuberculous meningitis
T2 - Diagnostic value and relationship to disease severity and outcome
AU - Simmons, Cameron P.
AU - Thwaites, Guy E.
AU - Quyen, Nguyen Than Ha
AU - Torok, Estee
AU - Hoang, Dang Minh
AU - Chau, Tran Thi Hong
AU - Mai, Pham Phuong
AU - Lan, Nguyen Thi Ngoc
AU - Dung, Nguyen Huy
AU - Quy, Hoang Thi
AU - Bang, Nguyen Duc
AU - Hien, Tran Tinh
AU - Farrar, Jeremy
PY - 2006/2/1
Y1 - 2006/2/1
N2 - Tuberculous meningitis (TBM) is the most devastating form of tuberculosis. Both intracerebral and peripheral blood immune responses may be relevant to pathogenesis, diagnosis, and outcome. In this study, the relationship between pretreatment host response, disease phenotype, and outcome in Vietnamese adults with TBM was examined. Before treatment, peripheral blood IFN-γ ELISPOT responses to the Mycobacterium tuberculosis Ags ESAT-6, CFP-10, and purified protein derivative (PPD) were a poor diagnostic predictor of TBM. Cerebrospinal fluid IL-6 concentrations at presentation were independently associated with severe disease presentation, suggesting an immunological correlate of neurological damage before treatment. Surprisingly however, elevated cerebrospinal fluid inflammatory cytokines were not associated with death or disability in HIV-negative TBM patients at presentation. HIV coinfection attenuated multiple cerebrospinal fluid inflammatory indices. Low cerebrospinal fluid IFN-γ concentrations were independently associated with death in HIV-positive TBM patients, implying that IFN-γ contributes to immunity and survival. Collectively, these results reveal the effect of HIV coinfection on the pathogenesis of TBM and suggest that intracerebral immune responses, at least in HIV-negative cases, may not be as intimately associated with disease outcome as previously thought.
AB - Tuberculous meningitis (TBM) is the most devastating form of tuberculosis. Both intracerebral and peripheral blood immune responses may be relevant to pathogenesis, diagnosis, and outcome. In this study, the relationship between pretreatment host response, disease phenotype, and outcome in Vietnamese adults with TBM was examined. Before treatment, peripheral blood IFN-γ ELISPOT responses to the Mycobacterium tuberculosis Ags ESAT-6, CFP-10, and purified protein derivative (PPD) were a poor diagnostic predictor of TBM. Cerebrospinal fluid IL-6 concentrations at presentation were independently associated with severe disease presentation, suggesting an immunological correlate of neurological damage before treatment. Surprisingly however, elevated cerebrospinal fluid inflammatory cytokines were not associated with death or disability in HIV-negative TBM patients at presentation. HIV coinfection attenuated multiple cerebrospinal fluid inflammatory indices. Low cerebrospinal fluid IFN-γ concentrations were independently associated with death in HIV-positive TBM patients, implying that IFN-γ contributes to immunity and survival. Collectively, these results reveal the effect of HIV coinfection on the pathogenesis of TBM and suggest that intracerebral immune responses, at least in HIV-negative cases, may not be as intimately associated with disease outcome as previously thought.
UR - http://www.scopus.com/inward/record.url?scp=31144477459&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.176.3.2007
DO - 10.4049/jimmunol.176.3.2007
M3 - Article
VL - 176
SP - 2007
EP - 2014
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -