Association of leprosy with <i>HLA-DRB1</i> in an Argentinean population

Borrás, Silvia García; Cotorruelo, Carlos; Racca, Liliana; Recarte, Mónica; Garcías, Celeste; Biondi, Claudia; Racca, Amelia

doi:10.1258/acb.2007.007156

Cited by 7 publications

(8 citation statements)

References 3 publications

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“…Studies of associations between HLA type and recognition of ESAT-6 among tuberculosis patients have noted that individual epitopes can be presented by diverse HLA types to human T cells, as well as that a given HLA type can present distinct epitopes [21, 22]. Our findings support earlier evidence of humoral responses to mycobacterial antigens [12, 23], and with the published literature regarding HLA specificity for mycobacterial antigens in tuberculosis and leprosy—two kindred granulomatous disorders [24–27]. …”

Section: Discussionsupporting

confidence: 89%

“…Studies of HLA associations with tuberculosis and lepromatous antigens reveal that most antigens are recognized in association with HLA-DR molecules (serologically defined as HLA-DR1 to HLA-DR10) [24–27]. HLA molecules encoded by HLA-DRB3 (HLA-DR52) and HLA-DRB4 (HLA-DR53) are also noted to be important in presentation of antigens from Mycobacterium tuberculosis and Mycobacterium leprae to Th-1 cells [27]. …”

Section: Discussionmentioning

confidence: 99%

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Mycobacterial ESAT-6 and katG are Recognized by Sarcoidosis CD4+ T Cells When Presented by the American Sarcoidosis Susceptibility Allele, DRB1*1101

et al. 2009

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IntroductionGenetic associations of American sarcoidosis susceptibility implicate MHC class II allele, DRB1*1101. We previously reported immune recognition of Mycobacterium peptides from peripheral cells of 26 sarcoidosis subjects, 24 PPD− healthy volunteers, and eight with latent tuberculosis infection.Materials and MethodsIn order to further link these genetic and immunologic pillars of sarcoidosis pathogenesis, we performed flow cytometry on these same subjects to identify the cells responsible for immune responses to ESAT-6 and katG peptides, followed by HLA typing to determine allelic associations with recognition.Discussion and ConclusionSarcoidosis CD4+ T cells were primarily responsible for the systemic responses. Recognition was inhibited by monoclonal antibody against HLA-DR and HLA-DQ, but not HLA-DP. Immune recognition of ESAT-6 peptide NNALQNLARTISEAG was associated with possession of DRB1*1101. ESAT-6 and katG presented by antigen-presenting cells expressing DRB1*1101-induced Th-1 responses from sarcoidosis T cells, thus providing a mechanistic insight for the association of HLA DRB1*1101 with sarcoidosis, and sarcoidosis T cell interaction with microbial antigens.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Mycobacterial ESAT-6 and katG are Recognized by Sarcoidosis CD4+ T Cells When Presented by the American Sarcoidosis Susceptibility Allele, DRB1*1101

et al. 2009

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“…Risk for leprosy associated with the DRB1 * 10 allele has been described in Turkish, Vietnamese, and Brazilian populations [17, 36], whereas the HLA-DRB1 * 14 allele was associated with the TT group in a population from north-eastern Brazil [42] and DRB1 * 14:01 and DRB1 * 14:06 were associated with leprosy per se in Argentinean population [37]. A protective effect on leprosy has been described for DRB1 * 04 in Brazilian, Korean, Japanese, Vietnamese, Argentinean, and Taiwanese populations [13, 30, 34, 36, 40].…”

Section: Classical Hla Class II Genesmentioning

confidence: 99%

Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

Jarduli

Sell

Reis

et al. 2013

BioMed Research International

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Many genes including HLA, KIR, and MICA genes, as well as polymorphisms in cytokines have been investigated for their role in infectious disease. HLA alleles may influence not only susceptibility or resistance to leprosy, but also the course of the disease. Some combinations of HLA and KIR may result in negative as well as positive interactions between NK cells and infected host cells with M. leprae, resulting in activation or inhibition of NK cells and, consequently, in death of bacillus. In addition, studies have demonstrated the influence of MICA genes in the pathogenesis of leprosy. Specifically, they may play a role in the interaction between NK cells and infected cells. Finally, pro- and anti-inflammatory cytokines have been influencing the clinical course of leprosy. Data from a wide variety of sources support the existence of genetic factors influencing the leprosy pathogenesis. These sources include twin studies, segregation analyses, family-based linkage and association studies, candidate gene association studies, and, most recently, genome-wide association studies (GWAS). The purpose of this brief review was to highlight the importance of some immune response genes and their correlation with the clinical forms of leprosy, as well as their implications for disease resistance and susceptibility.

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“…Table 1 summarizes both positive (association found) and negative (no association detected) association studies of leprosy for non-HLA candidate genes. A series of linkage and candidate gene studies has demonstrated associations of the major histocompatibility complex (MHC) class I and II loci (especially with HLA-DR2 alleles) with leprosy susceptibility (30,39,277,305,316,317,331,347). Those and other studies of the MHC region were extensively reviewed elsewhere previously (108,315) and will not be included in this review.…”

Section: Study Design For Complex Diseasesmentioning

confidence: 99%

“…While some studies support an association of the SNP GϪ308A with altered susceptibility to leprosy overall or leprosy type, the SNP appears to have opposite effects on leprosy polarity (tuberculoid versus lepromatous) in different populations. The TNF gene is located on chromosome 6q23-12 in a region in close linkage with HLA-DR (51, 187, 213 locus that has also been associated with leprosy (39,40,108,315,317). Similarly, the TNF Ϫ308 SNP is in LD with the LTA gene, and a haplotype containing the Ϫ308A allele and LTA SNPs ϩ10A, ϩ252G, and ϩ723A has been shown to be associated with increased LTA transcriptional activity (159).…”

Section: Cytokinesmentioning

confidence: 99%

Leprosy and the Human Genome

Misch¹,

Berrington²,

Vary

et al. 2010

Microbiol Mol Biol Rev

116

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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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Association of leprosy with HLA-DRB1 in an Argentinean population

Cited by 7 publications

References 3 publications

Mycobacterial ESAT-6 and katG are Recognized by Sarcoidosis CD4+ T Cells When Presented by the American Sarcoidosis Susceptibility Allele, DRB1*1101

Mycobacterial ESAT-6 and katG are Recognized by Sarcoidosis CD4+ T Cells When Presented by the American Sarcoidosis Susceptibility Allele, DRB1*1101

Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

Leprosy and the Human Genome

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