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Human leukocyte antigen associations with protection against tuberculosis infection and disease in human immunodeficiency virus-1 infected individuals, despite household exposure and immune suppression
Tuberculosis ( IF 2.8 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.tube.2020.102023
Faheem Seedat 1 , Ian James 2 , Shayne Loubser 3 , Ziyaad Waja 4 , Simon A Mallal 5 , Christopher Hoffmann 6 , Caroline T Tiemessen 3 , Richard E Chaisson 6 , Neil A Martinson 4
Affiliation  

BACKGROUND To determine the association of human leukocyte antigen (HLA) alleles as correlates of risk for and protection against tuberculin skin test (TST) positivity and active TB disease amongst HIV-infected adults. METHODS Genomic DNA was extracted from 754 HIV-infected adults whole-blood. HLA-A, -B, -C and -DRB1 loci were genotyped by next generation sequencing methods. HLA alleles were analysed by the presence/absence of TST immune conversion and active TB disease and further stratified by exposure to a household TB contact, CD4+ T-cell count and, for active TB disease, TST-positivity. RESULTS HLA-A*29:11 and - B*45:01/07 were associated with TST-positivity, while HLA-A*24:02, -A*29:02 and -B*15:16 with TST-negativity. In participants with a household TB contact, HLA-A*66:01, -A*68:02 and -B*49:01 were associated with TST-negativity. For TB disease, HLA-B*41:01, -C*06:02, -DRB1*04:01 and -DRB1*15:01 were associated with susceptibility, while HLA-B*07:02 and -DRB1*11:01 were protective, even for CD4+ T-cell count <350 cells/mm3. For initial TST-positivity and subsequent TB disease, HLA-A*01:01 and -DRB1*11:01 conveyed protection including for those with CD4+ T-cell count <350 cells/mm3. CONCLUSION Several HLA alleles are noted as correlates of TB infection, risk and natural protection in HIV-infected individuals. HLA associations may enable risk stratification of those with HIV infection. Protective alleles may assist in future TB vaccine development.

中文翻译:

尽管有家庭暴露和免疫抑制,人类白细胞抗原与人类免疫缺陷病毒 1 感染者预防结核病感染和疾病的关联

背景 确定人类白细胞抗原 (HLA) 等位基因与 HIV 感染成人中结核菌素皮肤试验 (TST) 阳性和活动性结核病的风险和预防相关性的关联。方法 从 754 名感染 HIV 的成年人全血中提取基因组 DNA。HLA-A、-B、-C 和-DRB1 位点通过下一代测序方法进行基因分型。通过是否存在 TST 免疫转换和活动性结核病来分析 HLA 等位基因,并通过接触家庭结核病接触者、CD4+ T 细胞计数和活动性结核病、TST 阳性进一步分层。结果 HLA-A*29:11 和 -B*45:01/07 与 TST 阳性相关,而 HLA-A*24:02、-A*29:02 和 -B*15:16 与 TST 阴性相关. 在有家庭结核病接触者的参与者中,HLA-A*66:01、-A*68:02 和 -B*49:01 与 TST 阴性相关。对于结核病,HLA-B*41:01、-C*06:02、-DRB1*04:01 和-DRB1*15:01 与易感性相关,而 HLA-B*07:02 和-DRB1*11 :01 具有保护作用,即使 CD4+ T 细胞计数 <350 个细胞/mm3。对于初始 TST 阳性和随后的结核病,HLA-A*01:01 和 -DRB1*11:01 提供保护,包括对 CD4+ T 细胞计数 <350 个细胞/mm3 的患者。结论 几个 HLA 等位基因被认为与 HIV 感染者的 TB 感染、风险和自然保护相关。HLA 关联可能有助于对 HIV 感染者进行风险分层。保护性等位基因可能有助于未来结核病疫苗的开发。对于初始 TST 阳性和随后的结核病,HLA-A*01:01 和 -DRB1*11:01 提供保护,包括对 CD4+ T 细胞计数 <350 个细胞/mm3 的患者。结论 几个 HLA 等位基因被认为与 HIV 感染者的 TB 感染、风险和自然保护相关。HLA 关联可能有助于对 HIV 感染者进行风险分层。保护性等位基因可能有助于未来结核病疫苗的开发。对于初始 TST 阳性和随后的结核病,HLA-A*01:01 和 -DRB1*11:01 提供保护,包括对 CD4+ T 细胞计数 <350 个细胞/mm3 的患者。结论 几个 HLA 等位基因被认为与 HIV 感染者的 TB 感染、风险和自然保护相关。HLA 关联可能有助于对 HIV 感染者进行风险分层。保护性等位基因可能有助于未来结核病疫苗的开发。
更新日期:2021-01-01
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