Quantitative Association Tests of Immune Responses to Antigens of Mycobacterium Tuberculosis: A Study of Twins in West Africa

<jats:title>Abstract</jats:title><jats:p>There is now considerable evidence that host genetic factors are important in determining the outcome of infection with <jats:italic>Mycobacterium tuberculosis</jats:italic> (MTB). The aim of this study was to assess the role of several candidate genes in the variation observed in the immune responses to MTB antigens. In-vitro assays of T-cell proliferation, an in-vivo intradermal delayed hypersensitivity response; cytokine and antibody secretions to several mycobacterial peptide antigens were assessed in healthy, but exposed, West African twins. Candidate gene polymorphisms were typed in the <jats:italic>NRAMP1</jats:italic>, <jats:italic>Vitamin D receptor</jats:italic>, <jats:italic>IL10</jats:italic>, <jats:italic>IL4</jats:italic>, <jats:italic>IL4 receptor</jats:italic> and <jats:italic>CTLA-4</jats:italic> genes. Variants of the loci <jats:italic>IL10</jats:italic> (−1082 G/A), <jats:italic>CTLA-4</jats:italic> (49 A/G) and the <jats:italic>IL4 receptor</jats:italic> (128 A/G) showed significant associations with immune responses to several antigens. T-cell proliferative responses and antibody responses were reduced, TNF-α responses were increased for subjects with the <jats:italic>CTLA-4</jats:italic> G allele. The T-cell proliferative responses of subjects with <jats:italic>IL10</jats:italic> GA and GG genotypes differed significantly. <jats:italic>IL4 receptor</jats:italic> AG and GG genotypes also showed significant differences in their T-cell proliferative responses to MTB antigens. These results yield a greater understanding of the genetic mechanisms that underlie the immune responses in tuberculosis and have implications for the design of therapeutic interventions.</jats:p>