Browsing by Author "Hanekom, W. A."

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    High heritability of antimycobacterial immunity in an area of hyperendemicity for tuberculosis disease
    (2010) Cobat, A.; Gallant, C. J.; Simkin, L.; Black, G. F.; Stanley, K.; Hughes, J.; Mark, Doherty T.; Hanekom, W. A.; Eley, B.; Beyers, Nulda; Jais, J.-P.; Van Helden, Paul D.; Abel, L.; Hoal, E. G.; Alcais, A.; Schurr, E.
    Human antimycobacterial immunity is a critical component of tuberculosis (TB) pathogenesis that is often used to infer the presence of TB infection. We report high heritability (>50%) for in vitro secretion of tumor necrosis factor α and interferon γ (IFN-γ), and the frequency of antigen-specific IFN-γ+CD4+ and IFN- γ+CD8+ cells in the response of whole blood to mycobacterial challenge. In principal component analysis, the first 3 components explain 78% of the overall variance consistent with the effect of pleiotropic regulatory genes of human antimycobacterial immunity. These results directly demonstrate the pivotal role played by host genetics in quantitative measures of antimycobacterial immunity underlying immune diagnosis of TB infection. © 2010 by the Infectious Diseases Society of America. All rights reserved.
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    Impact of age and sex on mycobacterial immunity in an area of high tuberculosis incidence
    (2010) Gallant, C. J.; Cobat, A.; Simkin, L.; Black, G. F.; Stanley, K.; Hughes, J.; Doherty, T. M.; Hanekom, W. A.; Eley, B.; Beyers, Nulda; Jais, J-P.; Van Helden, Paul D.; Abel, L.; Alcais, A.; Hoal, E. G.; Schurr, E.
    SETTING: The extent of immune reactivity measured by the tuberculin skin test (TST) and interferon-gamma (IFN-γ) T-cell assays is usually not analysed. OBJECTIVE: To determine the impact of age and sex on assay positivity and on the extent of reactivity of both TST and T-cell assays in young persons in an area of South Africa with high TB transmission. RESULTS: Age had a strong impact on assay positivity for all seven immune phenotypes tested (P < 0.0007). Among positive responders, the extent of purified protein derivative (PPD) triggered IFN-γ release (P < 0.003) was sensitive to age. ESAT-6 triggered IFN-γ release (day 7, P = 0.03) and the frequency of PPD-specific IFN-γ+CD4+ (P = 0.03) and IFN-γ+CD8+ cells (P = 0.04) were weakly dependent on age. By contrast, the extent of TST induration was insensitive to age (P > 0.05), and sex had no significant impact on any phenotype measured (P > 0.05). The high proportion of positive responders in the 1-10 year age-group observed with long-term whole blood assays, but not with 3-day assays and TST, suggests that long-term whole blood assays may be confounded by bacille Calmette-Guérin vaccination in this age group. CONCLUSION: There is a significant impact of age, but not sex, on different assays of immune reactivity in this high TB transmission setting. © 2010 The Union.