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

Published online by Cambridge University Press:  21 February 2012

Amanda Wiart
Affiliation:
Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom; Queensland Institute of Medical Research, Brisbane, Australia.
Annette Jepson
Affiliation:
Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom.
Winston Banya
Affiliation:
Medical Research Council Laboratories, Fajara, The Gambia.
Steve Bennett
Affiliation:
MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, United Kingdom.
Hilton Whittle
Affiliation:
MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, United Kingdom; Medical Research Council Laboratories, Fajara, The Gambia.
Nicholas G. Martin
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
Adrian V. S. Hill*
Affiliation:
Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom. [email protected]
*
*Address for correspondence: Adrian Hill, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.

Abstract

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There is now considerable evidence that host genetic factors are important in determining the outcome of infection with Mycobacterium 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 the NRAMP1, Vitamin D receptor, IL10, IL4, IL4 receptor and CTLA-4 genes. Variants of the loci IL10 (−1082 G/A), CTLA-4 (49 A/G) and the IL4 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 the CTLA-4 G allele. The T-cell proliferative responses of subjects with IL10 GA and GG genotypes differed significantly. IL4 receptor 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.

Type
Articles
Copyright
Copyright © Cambridge University Press 2004