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January - February 2011 HLA class II alleles as markers of tuberculosis susceptibility and resistance
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Vol. 17. Issue 1.
Pages 15-19 (January - February 2011)
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Vol. 17. Issue 1.
Pages 15-19 (January - February 2011)
DOI: 10.1016/S0873-2159(11)70005-8
Open Access
HLA class II alleles as markers of tuberculosis susceptibility and resistance
O papel do HLA classe II na susceptibilidade/resistência à tuberculose
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R. Duartea,b,c,
Corresponding author
rdmelo@med.up.pt

Corresponding author.
, C. Carvalhoa,d, C. Pereirad, A. Bettencourtd, A. Carvalhoa,c, M. Villare, A. Domingosf, H. Barrosb, J.A. Marquesb, P. Pinho Costag, D. Mendonçah, B. Martinsd,g
a Centro de Diagnóstico Pneumológico (CDP) de Vila Nova de Gaia, Vila Nova de Gaia, Portugal
b Faculdade de Medicina, Universidade do Porto, Portugal
c Centro Hospitalar de Vila Nova de Gaia/Espinho, Portugal
d Laboratório de Imunogenética, Instituto de Ciências Biomédicas Abe Salazar (ICBAS), Universidade do Porto, Porto, Portugal
e Centro de Diagnóstico Pneumológico (CDP) de Venda Nova, Lisboa, Portugal
f Centro Hospitalar Torres Vedras, Torres Vedras, Portugal
g Laboratório de Imunogenética, Instituto Nacional da Saúde (NSA) Dr. Ricardo Jorge, Porto, Portugal
h Departamento de Estudo de Populações, Instituto de Ciências Biomédicas Abe Salazar (ICBAS), Universidade do Porto, Porto, Portugal
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Abstract
Background

Not every individual exposed to Mycobacterium tuberculosis becomes infected. One host genetic factor, involved in modulating the immune response that has been studied in many ethnic groups is the association of human leukocyte antigens (HLA) with susceptibility to tuberculosis (TB).

 Objective

To investigate the association between TB, HLA-DRB1 and HLA-DQB1 alleles in a Portuguese population.

 Methods

HLA-DRB1 and HLA-DQB1 gene polymorphisms were analyzed by PCR-SSP in 92 TB patients, and 82 healthcare professionals without TB but exposed on a daily basis to infectious patients for more than two years (healthy exposed - HE). Tuberculin skin test reaction (TST), was positive in 69 individuals (all over 15mm) in the HE group (HE+) and negative in thirteen (HE—).

 Results

HLA-DRB1*14 frequency is higher in the TB patients group (7% vs. 0; p = 0.038) than in HE+.

 Conclusions

No genetic marker clearly indicative of disease susceptibility or resistance was identified in this study. However, HLA-DRB1*14 was more frequent in TB patients suggesting that it may be involved in the evolution infection towards active TB in our population.

Keywords:
HLA
Tuberculosis
Susceptibility
Resistance
Healthcare workers
Resumo
Introdução

Nem todos os indivíduos expostos ao Mycobacterium tuberculosis ficam infectados. Um dos factores genéticos envolvidos na modulação da resposta imune e estudado em muitos grupos étnicos é a associação entre moléculas HLA (human leukocyte antigens) e a susceptibilidade à tuberculose (TB).

 Objectivo

Investigar a relação entre TB e os alelos HLA-DRB1, DQB1 numa população Portuguesa.

 Métodos

Os polimorfismos dos genes HLA-DRB1 e HLA-DQB1 foram analisados por PCR-SSP em 92 doentes com TB e 82 profissionais de saúde saudáveis, expostos diariamente a doentes baciliferos por um período superior a 2 anos (expostos saudáveis: ES). Neste grupo de ES, o teste tuberculínico foi positivo (TST ≥ 10mm) em 69 indivíduos (todos com valor superior a 15mm) (ES+) e negativo (TST < 10mm) em 13 (ES—).

 Resultados

A frequência do alelo HLA-DRB1*14 é superior no grupo de doentes com tuberculose em relação ao grupo de ES+ (7% vs. 0; p=0,038).

 Conclusões

Não foi identificado neste estudo, nenhum marcador genético de susceptibilidade/resistência à doença. No entanto, o alelo HLA-DRB1*14 foi mais frequente nos doentes com tuberculose, sugerindo que possa estar envolvido na evolução da infecção para tuberculose activa na nossa população.

Palavras-chave:
HLA
Tuberculose
Susceptibilidade
Resistência
Profissionais de saúde
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