Pretreatment intracerebral and peripheral blood immune responses in vietnamese adults with tuberculous meningitis: Diagnostic value and relationship to disease severity and outcome

Cameron P. Simmons, Guy E. Thwaites, Nguyen Than Ha Quyen, Estee Torok, Dang Minh Hoang, Tran Thi Hong Chau, Pham Phuong Mai, Nguyen Thi Ngoc Lan, Nguyen Huy Dung, Hoang Thi Quy, Nguyen Duc Bang, Tran Tinh Hien, Jeremy Farrar

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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 languageEnglish
Pages (from-to)2007-2014
Number of pages8
JournalJournal of Immunology
Volume176
Issue number3
DOIs
Publication statusPublished - 1 Feb 2006

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