Gene Expression Profiling of Tuberculous Meningitis

BackgroundCellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism.MethodsWe studied 1069 Indonesian and Vietnamese adults with TBM (26.6% HIV-positive), 54 non-infectious controls, 50 with bacterial meningitis, and 60 with cryptococcal meningitis. Tryptophan and downstream metabolites were measured in cerebrospinal fluid (CSF) and plasma using targeted liquid chromatography mass-spectrometry. Individual metabolite levels were associated with survival, clinical parameters, CSF bacterial load and 92 CSF inflammatory proteins.ResultsCSF tryptophan was associated with 60-day mortality from tuberculous meningitis (HR=1.16, 95%CI=1.10-1.24, for each doubling in CSF tryptophan) both in HIV-negative and HIV-positive patients. CSF tryptophan concentrations did not correlate with CSF bacterial load nor CSF inflammation but were negatively correlated with CSF interferon-gamma concentrations. Unlike tryptophan, CSF concentrations of an intercorrelating cluster of downstream kynurenine metabolites did not predict mortality. These CSF kynurenine metabolites did however correlate with CSF inflammation and markers of blood-CSF leakage, and plasma kynurenine predicted death (HR 1.54, 95%CI=1.22-1.93). These findings were mostly specific for TBM, although high CSF tryptophan was also associated with mortality from cryptococcal meningitis.ConclusionTBM patients with a high baseline CSF tryptophan or high systemic (plasma) kynurenine are at increased risk of mortality. These findings may reveal new targets for host-directed therapy.FundingThis study was supported by National Institutes of Health (R01AI145781) and the Wellcome Trust (110179/Z/15/Z and 206724/Z/17/Z).

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Symptoms of AIDS Related Opportunistic Infections and Their Effects on Human Body

Jeevani¹

2013

J AIDS Clin Res

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HIV viruses have long term effects for the immune systems and further develop a number of varied illnesses such as fever, diarrhea, tuberculosis, pneumonia and skin infections. This condition is termed as AIDS Acquired Immune Deficiency Syndrome. Once the immune system is sufficiently weakened, such infections will develop and produce any of a wide range of symptoms. Some can be very severe some may lead to various cancers. There is no exact prediction for these symptoms. HIV testing is the only source to diagnose. The most difficult aspect of HIV/ AIDS is that though there are medicines, which can help with these illnesses but there is no vaccine and no cure for the HIV, so almost all the infected people become more and more ill and eventually die. It is important for every individual to know and understand about this infection. J o ur nal o f A ID S & Cli n ic a l R es earc h

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Gene Expression Profiling of Tuberculous Meningitis

Cited by 4 publications

References 41 publications

Improving host-directed therapy for tuberculous meningitis by linking clinical and multi-omics data

Improving host-directed therapy for tuberculous meningitis by linking clinical and multi-omics data

Tryptophan metabolism determines outcome in tuberculous meningitis: a targeted metabolomic analysis

Symptoms of AIDS Related Opportunistic Infections and Their Effects on Human Body

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