Class-I human leukocyte alleles in leprosy patients from Southern Brazil

Franceschi, Danilo Santana Alessio; Tsuneto, Luiza Tamie; Mazini, Priscila Saamara; Sacramento, William Sergio do; Reis, Pâmela Guimarães; Rudnick, Cristiane Conceição Chagas; Clementino, Samaia Laface; Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

doi:10.1590/s0037-86822011000500018

Cited by 10 publications

(7 citation statements)

References 24 publications

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“…The most common HLA types were the following: HLA-A ∗ 01, ∗ 02, ∗ 03, and ∗ 24 and HLA-B ∗ 15, ∗ 35, ∗ 44, and ∗ 51, similar to other previous reports in the north/northwest region of the State of Parana [ 19 ]; this was an important control to demonstrate that the population was representative.…”

Section: Resultssupporting

confidence: 88%

HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients

Sippert

Silva

Ayo

et al. 2015

Mediators of Inflammation

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Human leukocyte antigens (HLA) have a pivotal role in immune response and may be involved in antigen recognition of periodontal pathogens. However, the associations of HLA with chronic periodontitis (CP) have not been previously studied in the Brazilian population. In an attempt to clarify the issue of genetic predisposition to CP, we examined the distribution of HLA alleles, genotypes, and haplotypes in patients from Southern Brazil. One hundred and eight CP patients and 151 healthy and unrelated controls with age-, gender-, and ethnicity-matched were HLA investigated by polymerase chain reaction with sequence specific oligonucleotides. To exclude smoking as a predisposing factor, statistical analyses were performed in the total sample and in nonsmoking individuals. The significant results showed a positive association of the A∗02/HLA-B∗40 haplotype with CP (total samples: 4.2% versus 0%, P c = 0.03; nonsmokers: 4.3% versus 0%, P c = 0.23) and a lower frequency of HLA-B∗15/HLA-DRB1∗11 haplotype in CP compared to controls (total samples: 0.0% versus 4.3%, P c = 0.04; nonsmokers: 0 versus 5.1%, P c = 1.0). In conclusion, the HLA-A∗02/B∗40 haplotype may contribute to the development of CP, while HLA-B∗15/DRB1∗11 haplotype might indicate resistance to disease among Brazilians.

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Section: Resultssupporting

confidence: 88%

HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients

Sippert

Silva

Ayo

et al. 2015

Mediators of Inflammation

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“…Leprosy is still common in many tropical regions, South-East Asia being a notable hotbed of the disease (Reibel et al, 2015). Leprosy has exerted strong selective pressure on the human genome in general (Karlsson et al, 2014) and on the HLA region in particular (Chan, 1983; Franceschi et al, 2011; Shankarkumar, 2004; Shankarkumar et al, 2003; Takata et al, 1978; Zhang et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands

et al. 2017

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Summary HLA-B*46:01 was formed by an intergenic mini-conversion, between HLA-B*15:01 and HLA-C*01:02, in South-East Asia during the last 50,000 years and has since become the most common HLA-B allele in the region. A functional effect of the mini-conversion was introduction of the C1 epitope into HLA-B*46:01, making it an exceptional HLA-B allotype that is recognized by the C1-specific natural killer cell receptor KIR2DL3. High-resolution mass spectrometry showed that HLA-B*46:01 has a low diversity peptidome that is distinct from those of its parents. A minority (21%) of HLA-B*46:01 peptides, with common C-terminal characteristics, form ligands for KIR2DL3. The HLA-B*46:01 peptidome is predicted to be enriched for peptide antigens derived from Mycobacterium leprae. Overall, the results indicate that the distinctive peptidome and functions of HLA-B*46:01 provide carriers with resistance to leprosy, which drove its rapid rise in frequency in South-East Asia.

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“…In both analyses (compared to healthy controls and patient controls), HLA-B*58 and HLA-C*12 were associated with susceptibility to the BB form. HLA-C*12 was previously shown to be associated with susceptibility to leprosy per se in a population in Southeast Brazil [ 17 ]; however, no study has shown an association between HLA-B*58 and leprosy. Although our statistical analyses did not support susceptibility ( p c ≥ 0.05), the finding of HLA-B*58 in our patient group suggests that this allele is a specific marker for clinical BB leprosy in our region, as the frequency of this allele in the general population is approximately 5.0%, whereas in BB patients, the frequency was 11.36% [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil

et al. 2015

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BackgroundEvidence suggests that human leukocyte antigen (HLA) alleles influence the host immune response against Mycobacterium leprae. However, the association between HLA alleles and borderline (B) leprosy has not been studied. The aim of this study was to determine whether HLA class I and II molecules are associated with susceptibility or resistance to B leprosy including borderline-tuberculoid (BT), borderline-borderline (BB), and borderline-lepromatous (BL).MethodsDNA was obtained by the salting-out technique from the blood samples of 202 patients with B leprosy and 478 control subjects. HLA class I (A*, B*, and C* loci) and class II (DRB1* and DQB1* loci) genotypes were determined by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers.ResultsThe case-controlled analysis results showed a significant association between B leprosy and HLA-C*05 (5.94% vs. 14.02%; p = 0.002, OR = 0.38, 95% CI = 0.20–0.73, pc = 0.032) and HLA-DRB1*07 (16.34% vs. 26.77%; p = 0.003, OR = 0.53, 95% CI = 0.3–0.8, pc = 0.039). A protective association was observed between BL leprosy and HLA-DQB1*02 (18.18% vs. 39.53%; p = 0.005, OR = 0.34, 95% CI = 0.15–0.75, pc = 0.025). In reactional patients, a significant association was observed between HLA-B*15 (28.72% vs. 12.76%; p = 0.011, OR = 2.75, 95% CI = 1.30–5.85, pc = 0.352) and predisposition to reversal reaction. Haplotype analysis showed that A*02-B*07-C*07-DRB1*15-DQB1*06 (2.97% vs. 1.04%; p = 0.015) and A*02-B*40-C*03-DRB1*13-DQB1*06 (1.73% vs. 0.10%; p = 0.0011) were associated with susceptibility to the B form. The presence of the HLA-DRB1*02 or HLA-DRB1*03/HLA-DQB1*01 haplotypes in B patients (22.05% vs. 33.0%; p = 0.005) suggested the involvement of these haplotypes in this clinical form of the disease.ConclusionsThe results indicate the involvement of HLA class I and class II molecules in B leprosy and reversal reactions; it also suggest a role for HLA in polarization of the disease in this group of patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0751-0) contains supplementary material, which is available to authorized users.

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Class-I human leukocyte alleles in leprosy patients from Southern Brazil

Abstract: Although our results do not support the previous findings that HLA class-I alleles play a role in leprosy pathogenesis, we suggest new studies because of the importance of the association between the HLA and KIR in the innate immune response to leprosy.

Cited by 10 publications

References 24 publications

HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients

HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients

The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands

Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil

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