Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous Meningitis
| Autor: | Nguyen Van Vinh Chau, Nguyen Thuy Thuong Thuong, Nguyen Phu Huong Lan, Tran Thi Hong Chau, Trinh T. B. Tram, Sarah J. Dunstan, Nguyen Thi Hoang Mai, Vu T. N. Ha, Dorothee Heemskerk, Le Thi Phuong Thao, Lalita Ramakrishnan, Nguyen Duc Bang, Guy E. Thwaites, Maxine Caws, Marcel Wolbers |
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| Přispěvatelé: | Ramakrishnan, Lalita [0000-0003-0692-5533], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment qu_136 Antitubercular Agents HIV Infections Kaplan-Meier Estimate urologic and male genital diseases chemistry.chemical_compound Antiretroviral Therapy Highly Active Genotype Leukocytes Immunology and Allergy Aged 80 and over Epoxide Hydrolases Leukotriene A4 inflammatory response Middle Aged 3. Good health Infectious Diseases Cytokine Tuberculosis Meningeal Female wf_200 medicine.symptom survival Adult Adolescent qw_568 Inflammation Biology Polymorphism Single Nucleotide Tuberculous meningitis Proinflammatory cytokine Leukotriene-A4 hydrolase 03 medical and health sciences Young Adult Leukotriene A4 hydrolase genotype wl_200 Major Article medicine Humans Cerebrum Survival analysis Aged Proportional Hazards Models qu_500 Mycobacterium tuberculosis medicine.disease Survival Analysis cytokines 030104 developmental biology chemistry tuberculous meningitis Immunology Multivariate Analysis |
| Zdroj: | The Journal of Infectious Diseases |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Background.: Tuberculous meningitis (TBM) is the most devastating form of tuberculosis, yet very little is known about the pathophysiology. We hypothesized that the genotype of leukotriene A4 hydrolase (encoded by LTA4H), which determines inflammatory eicosanoid expression, influences intracerebral inflammation, and predicts survival from TBM. Methods.: We characterized the pretreatment clinical and intracerebral inflammatory phenotype and 9-month survival of 764 adults with TBM. All were genotyped for single-nucleotide polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal fluid (CSF) leukocyte and cytokine concentrations. Results.: LTA4H genotype predicted survival of human immunodeficiency virus (HIV)-uninfected patients, with TT-genotype patients significantly more likely to survive TBM than CC-genotype patients, according to Cox regression analysis (univariate P = .040 and multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF proinflammatory cytokine concentrations, with intermediate and lower concentrations in those with CT and CC genotypes. Increased CSF cytokine concentrations correlated with more-severe disease, but patients with low CSF leukocytes and cytokine concentrations were more likely to die from TBM. HIV infection independently predicted death due to TBM (hazard ratio, 3.94; 95% confidence interval, 2.79-5.56) and was associated with globally increased CSF cytokine concentrations, independent of LTA4H genotype. Conclusions.: LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from TBM. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals. |
| Databáze: | OpenAIRE |
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