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

AbstractThere is now considerable evidence that host genetic factors are important in determining the outcome of infection withMycobacterium tuberculosis(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 theNRAMP1,Vitamin D receptor,IL10,IL4,IL4 receptorandCTLA-4genes. Variants of the lociIL10(−1082 G/A),CTLA-4(49 A/G) and theIL4 receptor(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 theCTLA-4G allele. The T-cell proliferative responses of subjects withIL10GA and GG genotypes differed significantly.IL4 receptorAG 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.