HLA class II alleles as markers of tuberculosis susceptibility and resistance
O papel do HLA classe II na susceptibilidade/resistência à tuberculose
R. Duartea,b,c,
, 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
Corresponding author
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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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).</p></span> <span><span class="elsevierStyleSectionTitle">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To investigate the association between TB, HLA-DRB1 and HLA-DQB1 alleles in a Portuguese population.</p></span> <span><span class="elsevierStyleSectionTitle">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">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 15<span class="elsevierStyleHsp" style=""></span>mm) in the HE group (HE+) and negative in thirteen (HE—).</p></span> <span><span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">HLA-DRB1*14 frequency is higher in the TB patients group (7% vs. 0; p = 0.038) than in HE+.</p></span> <span><span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">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.</p></span>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span><span class="elsevierStyleSectionTitle">Introdução</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Nem todos os indivíduos expostos ao <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> ficam infectados. Um dos factores genéticos envolvidos na modulação da resposta imune e estudado em muitos grupos étnicos é a associação entre moléculas HLA <span class="elsevierStyleItalic">(human leukocyte antigens)</span> e a susceptibilidade à tuberculose (TB).</p></span> <span><span class="elsevierStyleSectionTitle">Objectivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Investigar a relação entre TB e os alelos HLA-DRB1, DQB1 numa população Portuguesa.</p></span> <span><span class="elsevierStyleSectionTitle">Métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">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 ≥ 10<span class="elsevierStyleHsp" style=""></span>mm) em 69 indivíduos (todos com valor superior a 15<span class="elsevierStyleHsp" style=""></span>mm) (ES+) e negativo (TST < 10<span class="elsevierStyleHsp" style=""></span>mm) em 13 (ES—).</p></span> <span><span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">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<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,038).</p></span> <span><span class="elsevierStyleSectionTitle">Conclusões</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">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.</p></span>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Dye" 1 => "S. Scheele" 2 => "P. 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| 2024 June | 27 | 25 | 52 |
| 2024 May | 30 | 32 | 62 |
| 2024 April | 41 | 34 | 75 |
| 2024 March | 24 | 31 | 55 |
| 2024 February | 35 | 33 | 68 |
| 2024 January | 21 | 37 | 58 |
| 2023 December | 28 | 24 | 52 |
| 2023 November | 21 | 31 | 52 |
| 2023 October | 17 | 41 | 58 |
| 2023 September | 27 | 35 | 62 |
| 2023 August | 21 | 19 | 40 |
| 2023 July | 21 | 27 | 48 |
| 2023 June | 19 | 23 | 42 |
| 2023 May | 29 | 20 | 49 |
| 2023 April | 23 | 15 | 38 |
| 2023 March | 27 | 28 | 55 |
| 2023 February | 25 | 40 | 65 |
| 2023 January | 19 | 16 | 35 |
| 2022 December | 23 | 19 | 42 |
| 2022 November | 45 | 39 | 84 |
| 2022 October | 32 | 19 | 51 |
| 2022 September | 13 | 39 | 52 |
| 2022 August | 37 | 45 | 82 |
| 2022 July | 25 | 45 | 70 |
| 2022 June | 16 | 34 | 50 |
| 2022 May | 32 | 32 | 64 |
| 2022 April | 24 | 42 | 66 |
| 2022 March | 21 | 40 | 61 |
| 2022 February | 25 | 36 | 61 |
| 2022 January | 21 | 33 | 54 |
| 2021 December | 22 | 36 | 58 |
| 2021 November | 19 | 32 | 51 |
| 2021 October | 33 | 39 | 72 |
| 2021 September | 30 | 26 | 56 |
| 2021 August | 33 | 23 | 56 |
| 2021 July | 21 | 30 | 51 |
| 2021 June | 23 | 22 | 45 |
| 2021 May | 27 | 36 | 63 |
| 2021 April | 51 | 87 | 138 |
| 2021 March | 55 | 12 | 67 |
| 2021 February | 39 | 17 | 56 |
| 2021 January | 22 | 9 | 31 |
| 2020 December | 42 | 18 | 60 |
| 2020 November | 38 | 24 | 62 |
| 2020 October | 23 | 29 | 52 |
| 2020 September | 69 | 32 | 101 |
| 2020 August | 87 | 16 | 103 |
| 2020 July | 120 | 18 | 138 |
| 2020 June | 85 | 20 | 105 |
| 2020 May | 97 | 14 | 111 |
| 2020 April | 77 | 23 | 100 |
| 2020 March | 57 | 19 | 76 |
| 2020 February | 71 | 50 | 121 |
| 2020 January | 81 | 18 | 99 |
| 2019 December | 64 | 18 | 82 |
| 2019 November | 78 | 17 | 95 |
| 2019 October | 71 | 18 | 89 |
| 2019 September | 78 | 22 | 100 |
| 2019 August | 114 | 21 | 135 |
| 2019 July | 89 | 23 | 112 |
| 2019 June | 110 | 26 | 136 |
| 2019 May | 140 | 38 | 178 |
| 2019 April | 73 | 42 | 115 |
| 2019 March | 135 | 31 | 166 |
| 2019 February | 137 | 29 | 166 |
| 2019 January | 132 | 33 | 165 |
| 2018 December | 99 | 23 | 122 |
| 2018 November | 36 | 0 | 36 |
| 2018 October | 41 | 5 | 46 |
| 2018 September | 32 | 9 | 41 |
| 2018 August | 22 | 30 | 52 |
| 2018 July | 25 | 27 | 52 |
| 2018 June | 26 | 19 | 45 |
| 2018 May | 70 | 19 | 89 |
| 2018 April | 44 | 36 | 80 |
| 2018 March | 64 | 41 | 105 |
| 2018 February | 34 | 12 | 46 |
| 2018 January | 64 | 19 | 83 |
| 2017 December | 103 | 21 | 124 |
| 2017 November | 37 | 16 | 53 |
| 2017 October | 25 | 14 | 39 |
| 2017 September | 17 | 11 | 28 |
| 2017 August | 13 | 23 | 36 |
| 2017 July | 10 | 9 | 19 |
| 2017 June | 32 | 22 | 54 |
| 2017 May | 25 | 10 | 35 |
| 2017 April | 7 | 1 | 8 |
| 2017 March | 13 | 2 | 15 |
| 2017 February | 12 | 3 | 15 |
| 2017 January | 12 | 5 | 17 |
| 2016 December | 23 | 6 | 29 |
| 2016 November | 10 | 3 | 13 |
| 2016 October | 9 | 7 | 16 |
| 2016 September | 6 | 2 | 8 |
| 2016 August | 5 | 2 | 7 |
| 2016 July | 5 | 5 | 10 |
| 2016 April | 50 | 1 | 51 |
| 2016 March | 62 | 23 | 85 |
| 2016 February | 77 | 23 | 100 |
| 2016 January | 53 | 20 | 73 |
| 2015 December | 58 | 17 | 75 |
| 2015 November | 48 | 15 | 63 |
| 2015 October | 56 | 16 | 72 |
| 2015 September | 57 | 12 | 69 |
| 2015 August | 57 | 16 | 73 |
| 2015 July | 66 | 8 | 74 |
| 2015 June | 49 | 14 | 63 |
| 2015 May | 63 | 15 | 78 |
| 2015 April | 103 | 10 | 113 |
| 2015 March | 87 | 11 | 98 |
| 2015 February | 103 | 11 | 114 |
| 2015 January | 102 | 6 | 108 |
| 2014 December | 106 | 8 | 114 |
| 2014 November | 122 | 6 | 128 |
| 2014 October | 119 | 8 | 127 |
| 2014 September | 121 | 10 | 131 |
| 2014 August | 115 | 12 | 127 |
| 2014 July | 137 | 8 | 145 |
| 2014 June | 128 | 6 | 134 |
| 2014 May | 119 | 5 | 124 |
| 2014 April | 114 | 8 | 122 |
| 2014 March | 116 | 11 | 127 |
| 2014 February | 125 | 11 | 136 |
| 2014 January | 118 | 18 | 136 |
| 2013 December | 121 | 7 | 128 |
| 2013 November | 111 | 6 | 117 |
| 2013 October | 117 | 10 | 127 |
| 2013 September | 87 | 13 | 100 |
| 2013 August | 149 | 28 | 177 |
| 2013 July | 143 | 20 | 163 |
| 2013 June | 89 | 9 | 98 |
| 2013 May | 86 | 5 | 91 |
| 2013 April | 84 | 20 | 104 |
| 2013 March | 78 | 9 | 87 |
| 2013 February | 86 | 22 | 108 |
| 2013 January | 108 | 18 | 126 |
| 2012 December | 70 | 14 | 84 |
| 2012 November | 68 | 22 | 90 |
| 2012 October | 27 | 14 | 41 |
| 2012 September | 19 | 10 | 29 |
| 2012 January | 507 | 0 | 507 |
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