Identification of a Major Locus, TNF1, That Controls BCG-Triggered Tumor Necrosis Factor Production by Leukocytes in an Area Hyperendemic for Tuberculosis

• Published in: Clinical infectious diseases Vol. 57; no. 7; pp. 963 - 970
• Main Authors: Cobat, Aurelie, Hoal, Eileen G., Gallant, Caroline J., Simkin, Leah, Black, Gillian F., Stanley, Kim, Jaïs, Jean-Philippe, Yu, Ting-Heng, Boland-Auge, Anne, Grange, Ghislain, Delacourt, Christophe, van Helden, Paul, Casanova, Jean-Laurent, Abel, Laurent, Alcaïs, Alexandre, Schurr, Erwin
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2013; Oxford University Press (OUP)
• Subjects: Adult; Analysis of Variance; and Commentaries; ARTICLES AND COMMENTARIES; Bacillus calmette guerin vaccine; Bacterial diseases; BCG Vaccine - administration & dosage; Biological and medical sciences; Chi-Square Distribution; Child; Chromosomes; Chromosomes, Human, Pair 11; Drug resistance; Drug therapy; Endemic Diseases; Family; Genetic loci; Genetic Pleiotropy; Genetics; Genomics; Human bacterial diseases; Human health and pathology; Humans; Infections; Infectious diseases; Interferon; Interferon-gamma - administration & dosage; Interferon-gamma Release Tests; Latent tuberculosis; Leukocytes; Leukocytes - drug effects; Leukocytes - immunology; Life Sciences; Linkage Disequilibrium; Medical sciences; Mycobacterium bovis - immunology; Mycobacterium tuberculosis; Phenotype; Phenotypic traits; Quantitative Trait Loci; South Africa - epidemiology; TNF inhibitors; Tuberculosis; Tuberculosis - blood; Tuberculosis - epidemiology; Tuberculosis - immunology; Tuberculosis and atypical mycobacterial infections; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factors; South Africa; Infection; Prevention; Tuberculosis; Tumor necrosis factor; Leukocyte; BCG; Bacteriosis; Check; Identification; Mycobacterial infection; pleiotropic locus; multivariate linkage analysis; TNF; tuberculosis

Background. Tumor necrosis factor (TNF) is a key immune regulator of tuberculosis resistance, as exemplified by the highly increased risk of tuberculosis disease among individuals receiving TNF-blocker therapy. Methods. We determined the extent of TNF production after stimulation with BCG or BCG plu...