The genetic hypothesis for susceptibility to lepromatous leprosy

Smith, David Glenn

doi:10.1007/bf00390238

Cited by 33 publications

(13 citation statements)

References 34 publications

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“…More recent studies have considered clinical status of leprosy in family members as well as age-of-onset effects. Smith (1979), in a complex segregation analysis of Filipino families in which at least one male offspring had lepromatous leprosy, found di.stributions consistent with autosomal recessive inheritance of susceptibility to lepromatous leprosy but argued in favor of a multifactorial hypothesis with heritability of about 80%. This illustrates a difficulty in human genetics methodology that has been noted by many authors (Reich etal.…”

Section: Pedigree Analysismentioning

confidence: 99%

HLA and Susceptibility to Leprosy

Serjeantson¹

1983

Immunological Reviews

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This review examines the evidence for involvement of MHC-associated factors in host immune response to Mycobacterium leprae, by collating HLA studies of sporadic and familial leprosy and discussing possible HLA-related immunological mechanisms in determining host response. Formal linkage analysis of 109 multiple-case families with data available for HLA haplotype segregation showed that under a three-allele recessive model for susceptibility to leprosy, linkage was observed between the HLA complex and a leprosy susceptibility locus at a recombination fraction of 20%. The significance of the linkage relationship was confined to families with at least two tuberculoid leprosy offspring and neither parent affected. When one parent was affected, with leprosy of any clinical type, lod scores could neither implicate nor exclude linkage between HLA and leprosy susceptibility and this apparent paradox can be explained by the presence of an additional, non-HLA linked susceptibility locus for leprosy.

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Section: Pedigree Analysismentioning

confidence: 99%

HLA and Susceptibility to Leprosy

Serjeantson¹

1983

Immunological Reviews

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“…The roles of hereditary and environmental factors in the determination of the occurrence and types of leprosy have long been debated. Among voluminous amounts of literature, the recent publication on segregation analysis by Smith [14] and the study on twins by Chakravartti and Vogel [l] clearly demonstrated the relative importance of the hereditary factors in the occurrence of the disease.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Immunogenetic Background of Japanese Leprosy Patients by the HLA System

Izumi¹,

Sugiyama²,

Matsumoto³

et al. 1982

Vox Sanguinis

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295 lepromatous and 74 tuberculoid leprosy patients were typed for HLA-A, -B and -C and compared to 110 healthy controls. It was found that frequency of HLA-B7 was significantly high and that of Bw54 was significantly low in lepromatous leprosy. HLA-DR and MT types were investigated in 84 lepromatous and 28 tuberculoid patients and compared to 55 controls. Both lepromatous and tuberculoid patients showed a marked increase in DR2 frequency. The relative risk is 8.7 and 5.9. Lepromatous leprosy showed an increase in frequency of MT1 and decreases in those of DRw9 and MT3 too.

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“…A number of segregation studies have been carried out for leprosy (1,3,84,117,171,241,275,280,289,327), several of which have detected the presence of a recessive or codominant mode of inheritance for leprosy overall or for nonlepromatous leprosy (1,84,117,171,289).…”

Section: Assessing the Genetic Contribution To Leprosy Riskmentioning

confidence: 99%

Leprosy and the Human Genome

Misch¹,

Berrington²,

Vary

et al. 2010

Microbiol Mol Biol Rev

115

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SUMMARY Despite the availability of effective treatment for several decades, leprosy remains an important medical problem in many regions of the world. Infection with Mycobacterium leprae can produce paucibacillary disease, characterized by well-formed granulomas and a Th1 T-cell response, or multibacillary disease, characterized by poorly organized cellular infiltrates and Th2 cytokines. These diametric immune responses confer states of relative resistance or susceptibility to leprosy, respectively, and have well-defined clinical manifestations. As a result, leprosy provides a unique opportunity to dissect the genetic basis of human in vivo immunity. A series of studies over the past 40 years suggests that host genes influence the risk of leprosy acquisition and the predilection for different clinical forms of the disease. However, a comprehensive, cellular, and molecular view of the genes and variants involved is still being assembled. In this article, we review several decades of human genetic studies of leprosy, including a number of recent investigations. We emphasize genetic analyses that are validated by the replication of the same phenotype in independent studies or supported by functional experiments demonstrating biological mechanisms of action for specific polymorphisms. Identifying and functionally exploring the genetic and immunological factors that underlie human susceptibility to leprosy have yielded important insights into M. leprae pathogenesis and are likely to advance our understanding of the immune response to other pathogenic mycobacteria. This knowledge may inform new treatment or vaccine strategies for leprosy or tuberculosis.

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The genetic hypothesis for susceptibility to lepromatous leprosy

Cited by 33 publications

References 34 publications

HLA and Susceptibility to Leprosy

HLA and Susceptibility to Leprosy

Analysis of the Immunogenetic Background of Japanese Leprosy Patients by the HLA System

Leprosy and the Human Genome

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