Pretreatment Intracerebral and Peripheral Blood Immune Responses in Vietnamese Adults with Tuberculous Meningitis: Diagnostic Value and Relationship to Disease Severity and Outcome

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.

A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis

“…34À36 Previous immunologic studies in our cohort of TBM patients found that cerebrospinal fluid (CSF) interleukin-6 concentrations were associated with the most severe disease. 37,38 Given the central role of TLR2 in mediating immune responses, it is possible that TLR2 genetic variants differentially regulate inflammatory pathways and influence the intra-cerebral inflammatory responses that determine severity and outcome of the disease.…”

Tuberculous Meningitis in Adults: A Review of a Decade of Developments Focusing on Prognostic Factors for Outcome

“…The blood-brain barrier is often damaged, reflected by a raised CSF:serum albumin ratio [31][32][33]. In HIV-negative patients, the concentration of lactate and protein are positively associated with TBM grade and clinical outcome [31]. Lactate is produced in hypoxic tissues, and high levels in CSF may reflect ischemic events in the brain.…”

“…Typically in TBM, the CSF shows a lymphocytic pleiocytosis and inflammatory indices (including TNF, IFN-g, IL-8, IL-10, matrix metalloproteinases, and their corresponding tissue inhibitors) are usually raised in the CSF in the acute phase of disease. The blood-brain barrier is often damaged, reflected by a raised CSF:serum albumin ratio [31][32][33]. In HIV-negative patients, the concentration of lactate and protein are positively associated with TBM grade and clinical outcome [31].…”

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

“…Misra et al studied both children and adults and identified stage, age, focal weakness, cranial nerve palsies, and hydrocephalus as predictors of mortality at 3 months (133). Interestingly, features such as presenting intracranial pressure (184), cytokines in the CSF (198), isoniazid or streptomycin resistance (214), and M. tuberculosis genotype (122) have been shown not to be predictive of a poor outcome.…”