Leprosy and the Human Genome

Abstract

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.

Media Edukasi Berbasis Cetak dan Digital Tentang Pengobatan Lepra dan Efek Samping Obat Mempermudah Pemahaman Penderita Lepra, Keluarga, Masyarakat dan Tenaga Kesehatan di Tanjung Pasir Tentang Lepra dan Terapinya

“…Bakteri ini memiliki kemampuan unik untuk memasuki syaraf (Jacobson & Krahenbuhl, 1999). Biasanya individu yang terkena infeksi kuman penyebab lepra ini akan hidup tanpa gejala penyakit lepra selama 5 hingga 20 tahun (Misch et al, 2010). Gejala yang berkembang biasanya meliputi granuloma saraf, saluran pernapasan, kulit, dan mata.…”

Association of genetic polymorphism of HLA-DRB1 antigens with the susceptibility to lepromatous leprosy

“…Evidence that host genes affect susceptibility to leprosy or its various clinical forms is supported by data from a wide variety of sources, including twin studies, segregation analyses, family-based linkage and association studies, candidate gene association studies and, most recently, genome-wide association studies (GWASs) (7,9). One recent genome-wide scan pinpointed chromosome 6p21 as a leprosy susceptibility locus (10).…”

“…Immunologically, the LL pole is characterized by a Th2 T-cell immune response, antibody complex formation, absence of granulomas and failure to restrain M. leprae growth. By contrast, the TT pole presents with a Th1 T-cell cytokine response, a vigorous T-cell response to M. leprae antigens and containment of the infection in well-formed granulomas (7).…”

Insights from animal models on the immunogenetics of leprosy: a review

“…Observations on human genetically identical twins with leprosy also suggest an innate predisposition for the infection and mirror the similarity in responses seen here among armadillo siblings (Alter et al 2011). Toll-like receptor (TLR): an important key for activation of the innate immune system is interaction with TLR -These highly conserved type 1 trans membrane proteins (Akira & Takeda 2004, Misch et al 2010 are expressed on different immune cells and recognize various pathogen-associated molecular patterns. TLR interaction can initiate an inflammatory response that augments killing or containment of invading organisms (Iwasaki & Medzhitov 2004) or activate signalling pathways that alter the expression of various chemokines and cytokines.…”

“…TLR interaction can initiate an inflammatory response that augments killing or containment of invading organisms (Iwasaki & Medzhitov 2004) or activate signalling pathways that alter the expression of various chemokines and cytokines. Polymorphisms in TLR alleles have been linked to susceptibility or resistance to a large range of microbial infections (de Diego et al 2007) and specific polymorphic loci on TLR-1, TLR-2 and TLR-4 have been linked with the host response to leprosy in humans (Misch et al 2010).…”