IL10 haplotype associated with tuberculin skin test response but not with pulmonary TB

• Published in: PloS one Vol. 4; no. 5; p. e5420
• Main Authors: Thye, Thorsten, Browne, Edmund N, Chinbuah, Margaret A, Gyapong, John, Osei, Ivy, Owusu-Dabo, Ellis, Brattig, Norbert W, Niemann, Stefan, Rüsch-Gerdes, Sabine, Horstmann, Rolf D, Meyer, Christian G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2009; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Anergy; Antigens; Base Sequence; Carriers; Case-Control Studies; Cloning; Cytokines; Dendritic cells; Disease susceptibility; Disease transmission; DNA Primers - genetics; Enzyme-linked immunosorbent assay; Ethics; Ethnic Groups - genetics; Ethnicity; Female; Genetic control; Genetic Predisposition to Disease; Genetic Variation; Genetics and Genomics/Genetics of Disease; Ghana; Haplotypes; HIV; Homozygote; Human immunodeficiency virus; Humans; Immune response; Immunity, Innate - genetics; Immunology/Genetics of the Immune System; Immunology/Immunity to Infections; Infections; Infectious Diseases/Bacterial Infections; Interleukin 1; Interleukin 10; Interleukin-10 - blood; Interleukin-10 - genetics; Interleukins; Lymphocytes; Male; Medical research; Medicine; Minority & ethnic groups; Mycobacterium tuberculosis; Pathogens; Patients; Plasma levels; Preeclampsia; Promoter Regions, Genetic; Rheumatoid arthritis; Science; Skin; Skin tests; Studies; Teaching hospitals; Trends; Tuberculin; Tuberculin Test; Tuberculosis; Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - transmission; Ghana; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005420

Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions -2849 , -1082 , -819 , and -592 and reconstructed the haplotypes. The IL10 low-producer haplotype -2849A/-1082A/-819C/-592C, compared to the high-producer haplotype -2849G/-1082G/-819C/-592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3-3.6) and PPD-positive controls (OR 2.09, CI 1.2-3.5). Lower IL-10 plasma levels in homozygous -2849A/-1082A/-819C/-592C carriers, compared to homozygous -2849G/-1082G/-819C/-592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy.