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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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References
[1.]
C. Dye, S. Scheele, P. Dolin, et al.
Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project.
JAMA, 282 (1999), pp. 677-686
Medline
[2.]
N.M. Parrish, J.D. Dick, W.R. Bishai.
Mechanisms of latency in Mycobacterium tuberculosis.
Trends Microbiol, 6 (1998), pp. 107-112
Medline
[3.]
A. Jepson, A. Fowler, W. Banya, et al.
Genetic regulation of acquired immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.
Infect Immun, 69 (2001), pp. 3989-3994
http://dx.doi.org/10.1128/IAI.69.6.3989-3994.2001 | Medline
[4.]
C.N. Classen, M. Warren, J. Richardson, et al.
Impact of social interactions in the community on the transmission of tuberculosis in a high incidence area.
Thorax, 54 (1999), pp. 136-140
Medline
[5.]
S. Gruenheid, E. Pinner, M. Desjardins, et al.
Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome.
J Exp Med, 185 (1997), pp. 717-730
Medline
[6.]
B.L. Riggs, T.V. Nguyen, L.J. Melton, et al.
The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women.
J Bone Miner Res, 10 (1995), pp. 991-996
http://dx.doi.org/10.1002/jbmr.5650100622 | Medline
[7.]
R. Bellamy, C. Ruwende, T. Corrah, et al.
Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene.
J Infect Dis, 179 (1999), pp. 721-724
http://dx.doi.org/10.1086/314614 | Medline
[8.]
S.J. Lewis, I. Baker, S.G. Davey.
Meta-analysis of vitamin D receptor polymorphisms and pulmonary tuberculosis risk.
Int J Tuberc Lung Dis, 9 (2005), pp. 1174-1177
Medline
[9.]
P. Selvaraj, U. Sriram, S. Mathan Kurian, et al.
Tumour necrosis factor alpha (-238 and -308) and beta gene polymorphisms in pulmonary tuberculosis: haplotype analysis with HLA-A, B and DR genes.
Tuberculosis (Edinb), 81 (2001), pp. 335-341
[10.]
L. Scola, A. Crivello, V. Marino, et al.
IL-10 and TNF-alpha polymorphisms in a sample of Sicilian patients affected by tuberculosis: implication for ageing and life span expectancy.
Mech Ageing Dev, 124 (2003), pp. 569-572
Medline
[11.]
H.B. Oral, F. Budak, E.K. Uzaslan, et al.
Interleukin-10 (IL-10) gene polymorphism as a potential host susceptibility factor in tuberculosis.
Cytokine, 35 (2006), pp. 143-147
http://dx.doi.org/10.1016/j.cyto.2006.07.015 | Medline
[12.]
M.I. Henao, C. Montes, S.C. París, et al.
Cytokine gene polymorphisms in Colombian patients with different clinical presentations of tuberculosis.
Tuberculosis (Edinb), 86 (2006), pp. 11-19
[13.]
R.J. Wilkinson, P. Patel, M. Llewelyn, et al.
Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis.
J Exp Med, 189 (1999), pp. 1863-1874
Medline
[14.]
Z. Lombard, et al.
Association of HLA-DR-DQ, and vitamin D receptor alleles and haplotypes with tuberculosis in the Venda of South Africa.
Hum Immunol, 67 (2006), pp. 643-654
http://dx.doi.org/10.1016/j.humimm.2006.04.008 | Medline
[15.]
A.E. Goldfeld, J.C. Delgado, S. Thim, et al.
Association of an HLA-DQ allele with clinical tuberculosis.
JAMA, 279 (1998), pp. 226-228
Medline
[16.]
S. Vejbaesya, N. Chierakul, K. Luangtrakool, et al.
Associations of HLA class II alleles with pulmonary tuberculosis in Thais.
Eur J Immunogenet, 29 (2002), pp. 431-434
Medline
[17.]
M. Ravikumar, V. Dheenadhayalan, K. Rajaram, et al.
Associations of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in south India.
Tuber Lung Dis, 79 (1999), pp. 309-317
Medline
[18.]
A.S. Low, I. Azmy, N. Sharaf, et al.
Association between two tumour necrosis factor intronic polymorphisms and HLA alleles.
Eur J Immunogenet, 29 (2002), pp. 31-34
Medline
[19.]
A.A. Amirzargar, A. Yalda, M. Hajabolbaghi, et al.
The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis.
Int J Tuberc Lung Dis, 8 (2004), pp. 1017-1021
Medline
[20.]
H.S. Kim, M.H. Park, E.Y. Song, et al.
Association of HLA-DR and HLA-DQ genes with susceptibility to pulmonary tuberculosis in Koreans: preliminary evidence of associations with drug resistance, disease severity, and disease recurrence.
Hum Immunol, 66 (2005), pp. 1074-1081
http://dx.doi.org/10.1016/j.humimm.2005.08.242 | Medline
[21.]
J.C. Delgado, A. Baena, S. Thim, et al.
Ethnic-specific genetic associations with pulmonary tuberculosis.
J Infect Dis, 186 (2002), pp. 1463-1468
http://dx.doi.org/10.1086/344891 | Medline
[22.]
A.E. Goldfeld.
Genetic susceptibility to pulmonary tuberculosis in Cambodia.
Tuberculosis (Edinb), 84 (2004), pp. 76-81
[23.]
Programa Nacional de Luta Contra a Tuberculose, Direcção Geral da Saúde. Tuberculose: dados preliminares de 2008 [in Portuguese]. Available from: http://www.dgs.pt
[24.]
EuroTB and the national coordinators for tuberculosis surveillance in the WHO European Region. Surveillance of tuberculosis in Europe. Report on tuberculosis cases notified in 2006. Saint-Maurice, France: Institut de veille sanitaire; March 2008. Available from: http://www.eurotb.org/rapports/2006/full_report.pdf
[25.]
R. Duarte, J. Amado, H. Lucas, et al.
Portuguese Society of Pulmonology. [Treatment of latent tuberculosis infection: update of guidelines, 2006] [Article in Portuguese].
Rev Port Pneumol, 13 (2007), pp. 397-418
Medline
[26.]
S.A. Miller, H.F. Dykes, D.D. Polesky.
A simple salting out procedure for extracting DNA from human nucleated cells.
Nucleic Acids Res, 16 (1988), pp. 1215
Medline
[27.]
O. Olerup, A. Aldener, A. Fogdell.
HLA-DQB1 and -DQA1 typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours.
Tissue Antigens, 41 (1993), pp. 119-134
Medline
[28.]
A. Morais, H. Alves, B. Lima, et al.
HLA class I and II and TNF-alpha gene polymorphisms in sarcoidosis patients.
Rev Port Pneumol, 14 (2008), pp. 727-746
Medline
[29.]
G. Ruggiero, E. Consntini, D. Zanzi.
Allelic distribution of human leucocyte antigen in historical and recently diagnosed tuberculosis patients in Southern Italy.
Immunology, 111 (2004), pp. 318-322
Medline
[30.]
H. Mahmoudzadeh-Niknam, G. Khalili, P. Fadavi.
Allelic distribution of human leukocyte antigen in Iranian patients with pulmonary tuberculosis.
Hum Immunol, 64 (2003), pp. 124-129
Medline
[31.]
A.G. Matrashkin, E.M. Mes’ko, L.E. Pospelov, et al.
[Examining the distribution of HLA antigens in patients with tuberculosis and in healthy individuals in the Erza District, Republic of Tyva].
Probl Tuberk, 12 (2002), pp. 15-16
Medline
[32.]
R.A. Cox, M. Downs, R.E. Neimes, et al.
Immunogenetic analysis of human tuberculosis.
J Infect Dis, 158 (1988), pp. 1302-1308
Medline
[33.]
A. Dubaniewicz, G. Moszkowska, Z. Szczerkowska.
Frequency of DRB1-DQB1 two-locus haplotypes in tuberculosis: preliminary report.
Tuberculosis (Edinb), 85 (2005), pp. 259-267
[34.]
R. Rani, M.A. Fernandez-Vina, P. Stastny.
Associations between HLA class II alleles in a North Indian population.
Tissue Antigens, 52 (1998), pp. 37-43
Medline
[35.]
D. Teran-Escandon, L. Terán-Ortiz, A. Camarena-Olvera, et al.
Human leukocyte antigen-associated susceptibility to pulmonary tuberculosis: molecular analysis of class II alleles by DNA amplification and oligonucleotide hybridization in Mexican patients.
Chest, 115 (1999), pp. 428-433
Medline
[36.]
C.F. Reyn, C.R. Horsburgh, K.N. Olivier, et al.
Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States.
Int J Tuberc Lung Dis, 12 (2001), pp. 1122-1128
Medline
[37.]
Edwards LB, Acquaviva FA, Livesay VT. Identification of tuberculosis infected: Dual tests and density of reaction. Am Rev Resp Dis. 197;108:1334–9.
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