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

BACKGROUND: Evidence 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 mo...

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Autores principales: de Souza-Santana, Fabiana Covolo, Marcos, Elaine Valim Camarinha, Nogueira, Maria Esther Salles, Ura, Somei, Tomimori, Jane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307149/
https://www.ncbi.nlm.nih.gov/pubmed/25605482
http://dx.doi.org/10.1186/s12879-015-0751-0
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author de Souza-Santana, Fabiana Covolo
Marcos, Elaine Valim Camarinha
Nogueira, Maria Esther Salles
Ura, Somei
Tomimori, Jane
author_facet de Souza-Santana, Fabiana Covolo
Marcos, Elaine Valim Camarinha
Nogueira, Maria Esther Salles
Ura, Somei
Tomimori, Jane
author_sort de Souza-Santana, Fabiana Covolo
collection PubMed
description BACKGROUND: Evidence 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). METHODS: DNA 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. RESULTS: The 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. CONCLUSIONS: The 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 MATERIAL: The 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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spelling pubmed-43071492015-01-28 Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil de Souza-Santana, Fabiana Covolo Marcos, Elaine Valim Camarinha Nogueira, Maria Esther Salles Ura, Somei Tomimori, Jane BMC Infect Dis Research Article BACKGROUND: Evidence 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). METHODS: DNA 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. RESULTS: The 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. CONCLUSIONS: The 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 MATERIAL: The online version of this article (doi:10.1186/s12879-015-0751-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-21 /pmc/articles/PMC4307149/ /pubmed/25605482 http://dx.doi.org/10.1186/s12879-015-0751-0 Text en © de Souza-Santana et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
de Souza-Santana, Fabiana Covolo
Marcos, Elaine Valim Camarinha
Nogueira, Maria Esther Salles
Ura, Somei
Tomimori, Jane
Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil
title Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil
title_full Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil
title_fullStr Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil
title_full_unstemmed Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil
title_short Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil
title_sort human leukocyte antigen class i and class ii alleles are associated with susceptibility and resistance in borderline leprosy patients from southeast brazil
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307149/
https://www.ncbi.nlm.nih.gov/pubmed/25605482
http://dx.doi.org/10.1186/s12879-015-0751-0
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