Human Leukocyte Antigen (HLA)-Linked Control of Susceptibility to Pulmonary Tuberculosis and Association with HLA-DR Types

Singh, Shruti; Nk, Mehra; Dingley, H. B.; Pande, J. N.; Vaidya, M. C.

doi:10.1093/infdis/148.4.676

Cited by 133 publications

(59 citation statements)

References 21 publications

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“…A variety of different approaches have previously been used to identify genes involved in host susceptibility to infectious diseases, including candidate gene studies on tuberculosis (8,9,31) and malaria (32) and studies on inbred families with extreme susceptibility to non-tuberculous mycobacteria (33). To date, linkage studies have addressed only candidate genes or small numbers of extended families with measurements of schistosomal parasite burdens rather than disease (34,35).…”

Section: Discussionmentioning

confidence: 99%

Genetic susceptibility to tuberculosis in Africans: A genome-wide scan

Bellamy

Beyers

McAdam

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

268

185

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Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod ‫؍‬ 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

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Section: Discussionmentioning

confidence: 99%

Genetic susceptibility to tuberculosis in Africans: A genome-wide scan

Bellamy

Beyers

McAdam

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

268

185

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“…Human Leucocyte Antigen (HLA) genes are implicated in the spectral clinical manifestations characteristic of both tuberculosis and leprosy [119]. The limited data obtained may indicate an association of HLA-DR2 and pulmonary tuberculosis [120,121]. In mice, H-2 linked genes are known to control both granulomatous responses and resistance to M. lepramurium [122].…”

Section: Genetic Factors In Resistance To Tuberculosismentioning

confidence: 99%

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

1997

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Andersen P. Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis. Scand J Immunol 1997;45:115-131 Tuberculosis (TB) is the largest single infectious cause of human mortality. The incidence of TB has remained high in most of the developing world and the disease has recently re-emerged as a public health problem in industrialized countries. The development of a new improved TB vaccine is a highly prioritized international research area, which has been further stimulated by the appearance of multi-drug resistant strains of Mycobacterium tuberculosis. The present status of the attempts to characterize the protective immune response to TB will be reviewed with special emphasis on recent progress in the identification and characterization of target molecules recognized by protective cells. This paper will focus on proteins released from live bacteria and discuss their role in the host-pathogen interaction and the ongoing attempts to use these molecules in TB subunit vaccines.

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“…30 However, we are not aware of previous reports of gene-environment interactions affecting susceptibility to an infectious disease. HLA alleles have been associated with susceptibility to other infectious pathogens 13,14 including P. malariae, 31,32 M. tuberculosis [33][34][35] and HIV. [36][37][38][39][40][41] These associations are often attributed to changes in T-cell response caused by modified interaction between the variant HLA allele and antigenic peptides.…”

Section: Resultsmentioning

confidence: 99%