RESUMEN
The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.
Asunto(s)
Proteínas Portadoras/genética , Proteínas de Transporte de Catión , Predisposición Genética a la Enfermedad , Lepromina/inmunología , Lepra/inmunología , Proteínas de la Membrana/genética , Piel/inmunología , China/etnología , Femenino , Ligamiento Genético , Granuloma , Haplotipos , Humanos , Inmunidad Innata , Inyecciones Intradérmicas , Lepra Lepromatosa/inmunología , Lepra Tuberculoide/inmunología , Masculino , Núcleo Familiar , Linaje , Fenotipo , Linfocitos T Colaboradores-Inductores , VietnamRESUMEN
The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.
Asunto(s)
Masculino , Femenino , Humanos , Lepromina/inmunología , China/etnología , Granuloma , Lepra Tuberculoide/inmunología , Lepra Lepromatosa/inmunología , Lepra/inmunología , Piel/inmunología , Vietnam , Fenotipo , Haplotipos , Inmunidad Innata , Inyecciones Intradérmicas , Linfocitos T Colaboradores-Inductores , Linaje , Núcleo FamiliarRESUMEN
Leprosy is a debilitating infectious disease of human skin and nerves. Genetic factors of the host play an important role in the manifestation of disease susceptibility. The human NRAMP1 gene is a leprosy susceptibility candidate locus since its murine homologue Nramp1 (formerly Lsh/Ity/Bcg) controls innate resistance to Mycobacterium lepraemurium. In this study, 168 members of 20 multiplex leprosy families were genotyped for NRAMP1 alleles and 4 closely linked polymorphic markers. Highly informative haplotypes overlapping the NRAMP1 gene were constructed, and the haplotype segregation into leprosy-affected offspring was analyzed. It was observed that the segregation of NRAMP1 haplotypes into affected siblings was significantly nonrandom. This finding is consistent with the hypothesis that NRAMP1 itself is a leprosy susceptibility locus.
Asunto(s)
Proteínas Portadoras/genética , Proteínas de Transporte de Catión , Predisposición Genética a la Enfermedad , Lepra/genética , Proteínas de la Membrana/genética , Alelos , Marcadores Genéticos , Haplotipos/genética , Interacciones Huésped-Parásitos/genética , Humanos , Linaje , Polimorfismo GenéticoRESUMEN
A case-control study was conducted to assess the protective effect of intradermal BCG against leprosy and its subtypes in southern Vietnam. A total of 177 cases were selected with a distribution by subtypes as follows: 38 TT, 23 BT, 51 BB, 36 BL, 22 LL, and 7 indeterminate. Two controls were matched with a case for age, sex, ethnic group, socioeconomic status, and district area. The odds ratio assessing the protective effect of BCG varied from 0.44 (0.19-1.03) in the BB subtype to 3.00 (0.24-37.5) in indeterminate leprosy; whereas its overall value was 0.71 (0.45-1.10) for leprosy per se. When all borderline leprosy types were pooled, the protective effect of BCG was found significant with an odds ratio of 0.48 (0.27-0.84). In the polar forms of leprosy, TT and LL, the odds ratio was > 1 with large confidence intervals. It is possible that BCG induces a shift in the immune response to a higher level of cell-mediated immunity. When BCG vaccination is given after primary infection with Mycobacterium leprae, this shift could be the cause of an increase in the risk of the occurrence of milder and transient forms of the disease. In TT forms BCG might reinforce the preexisting subclinical immunopathological reactions, and in stable LL forms BCG might be unable to induce any protective form of immunity. These results confirm the important variability in the protection offered by BCG with respect to the different types of leprosy, and may have important implications for the design and the interpretation of vaccine trials that should take into account the respective proportions of leprosy forms observed in the study region.