High heritability of antimycobacterial immunity in an area of hyperendemicity for tuberculosis disease.
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.
Cobat
Aurelie
A
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Gallant
Caroline J
CJ
Simkin
Leah
L
Black
Gillian F
GF
Stanley
Kim
K
Hughes
Jane
J
Doherty
T Mark
TM
Hanekom
Willem A
WA
Eley
Brian
B
Beyers
Nulda
N
Jaïs
Jean-Philippe
JP
van Helden
Paul
P
Abel
Laurent
L
Hoal
Eileen G
EG
Alcaïs
Alexandre
A
Schurr
Erwin
E
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
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma