title: High heritability of antimycobacterial immunity in an area of hyperendemicity for tuberculosis disease.
abstract: 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 alpha and interferon gamma (IFN-gamma), and the frequency of antigen-specific IFN-gamma(+)CD4(+) and IFN-gamma(+)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.
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France.
authors: Aurelie
authors: A
authors: Cobat
authors: Caroline J
authors: CJ
authors: Gallant
authors: Leah
authors: L
authors: Simkin
authors: Gillian F
authors: GF
authors: Black
authors: Kim
authors: K
authors: Stanley
authors: Jane
authors: J
authors: Hughes
authors: T Mark
authors: TM
authors: Doherty
authors: Willem A
authors: WA
authors: Hanekom
authors: Brian
authors: B
authors: Eley
authors: Nulda
authors: N
authors: Beyers
authors: Jean-Philippe
authors: JP
authors: Jaïs
authors: Paul
authors: P
authors: van Helden
authors: Laurent
authors: L
authors: Abel
authors: Eileen G
authors: EG
authors: Hoal
authors: Alexandre
authors: A
authors: Alcaïs
authors: Erwin
authors: E
authors: Schurr
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D019353:Endemic Diseases; D005260:Female; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010641:Phenotype; D025341:Principal Component Analysis; D013019:South Africa; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma