Associations between MHC class I and susceptibility to HIV-2 disease progression
Associations between MHC class I and susceptibility to HIV-2 disease progression
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DOI：
10.1097/01.qhv.0000021465.39141.02
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发表时间：
2002-01-01
期刊：
影响因子：
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通讯作者：
Kanki, P
中科院分区：
文献类型：
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作者：
Diouf, K;Sarr, AD;Kanki, P
目的：2 型人类免疫缺陷病毒 (HIV-2) 的疾病进展速度明显慢于 1 型人类免疫缺陷病毒 (HIV-1)。据推测，与 HIV-1 相比，疾病进展易感性的遗传决定因素在这种感染中发挥着更重要的作用。我们试图鉴定塞内加尔人群中常见的人类淋巴细胞抗原 (HLA) 等位基因，并比较疾病进展低风险和高风险的 HIV-2 感染者之间的 HLA 图谱。 研究设计/方法：我们进行了一项病例对照研究，调查 MHC I 类基因与 HIV-2 感染者疾病进展风险之间可能存在的关联。使用序列特异性引物聚合酶链反应 (PCR-SSP) 对来自塞内加尔达喀尔队列的 62 名女性性工作者进行了 MHC I 类基因型的分子定义。 HIV-2 抗原 p26 抗体的缺乏先前已被证明可以预测疾病进展，并在本研究中用作替代标记。确定 21 例患者缺乏 p26 抗体，因此疾病进展风险较高，并与随机选择的 41 例 p26 抗体阳性对照进行比较。结果：统计分析显示，HLA B35 与缺乏 p26 抗体和疾病进展风险较高显着相关（p < 0.05）。对于自定义 I 类单倍型 B35-Cw4 和 A23-Cw7 也发现了相同的关联（p < 0.05）。 HLA B53 等位基因与较慢的疾病进展有关；然而，这种关联在统计上并不显着。我们观察到杂合子 HIV-2 疾病进展风险较低的趋势，正如之前在 HIV-1 疾病中报道的那样。结论：在这个西非人群中，观察到 HLA I 类等位基因的独特特征，其中许多等位基因似乎影响 HIV-2 感染的疾病进展。
Objectives: Human immunodeficiency virus type 2 (HIV-2) progression to disease is significantly slower than that of human immunodeficiency virus type 1 (HIV-1). Genetic determinants for susceptibility to disease progression were hypothesized to play a more significant role in this infection compared with HIV-1. We sought to identify common human lymphocyte antigen (HLA) alleles in the Senegalese population and to compare HLA profiles between HIV-2-infected individuals with low and high risk for disease progression.Study Design/Methods: We conducted a case-control study investigating possible associations between MHC class I genes and the risk of disease progression in HIV-2-infected individuals. The MHC class I genotype was molecularly defined using polymerase chain reaction with sequence specific primers (PCR-SSP) in 62 female sex workers from the Dakar, Senegal cohort. Lack of antibodies to the HIV-2 antigen p26 has been previously shown to predict disease progression and was used in this study as a surrogate marker. Twenty-one cases were identified lacking antibodies to p26, therefore at a higher risk of disease progression, and were compared with 41 p26 antibody-positive, randomly selected controls.Results: Statistical analysis showed that HLA B35 was significantly associated with lack of p26 antibodies, and higher risk of disease progression (p < 0.05). The same association was found for the self-defined class I haplotypes B35-Cw4 and A23-Cw7 (p < 0.05). The HLA B53 allele was associated with slower disease progression; however, this association was not statistically significant. We observed a trend whereby heterozygotes were at lower risk for HIV-2 disease progression, as previously reported in HIV-1 disease.Conclusions: In this West African population, a distinct profile of HLA class I alleles was observed, and many of these appear to influence disease progression in HIV-2 infection.