The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type T infection
The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type T infection
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DOI：
10.4049/jimmunol.165.12.7278
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发表时间：
2000-12-15
影响因子：
4.4
通讯作者：
Bangham, CRM
中科院分区：
文献类型：
--
作者：
Jeffery, KJM;Siddiqui, AA;Bangham, CRM
炎性疾病人类T细胞嗜淋巴细胞病毒I型（HTLV-I）相关的脊髓病（HAM/TSP）仅发生在1-2%的HTLV-I感染个体中，并且与HTLV-I的高前病毒负荷相关。我们假设一个人发展HAM/TSP的风险取决于他们对病毒的免疫应答的效率，由于影响这种反应的基因的多态性，个体之间的反应不同。之前我们表明，拥有HLA-A*02与HAM/TSP的较低风险以及健康HTLV-I携带者的较低前病毒载量相关。然而，HLA-A*02并不能解释HAM/TSP风险的所有观察到的差异。在此，我们在日本的相同研究人群中提供了证据，表明HLA-Cw*08也与疾病保护相关（概率值，双尾检验= 0.002），并且在健康携带者中具有较低的前病毒负荷。拥有A*02和/或Cw*08基因可预防36%的潜在HAM/TSP病例。相反，HLA-B*5401与HAM/TSP患者的较高易感性（概率值，双尾检验= 0.0003）和较高的前病毒载量相关。在给定的前病毒负荷下，B*5401似乎增加了疾病的风险。可归因于B*5401的HAM/TSP病例的比例为17%。此外，在所有三个HLA I类基因座上杂合的个体比在一个或多个基因座上纯合的个体具有较低的HTLV-I前病毒载量。这些结果与对HTLV-I的强I类限制性CTL应答降低提议负荷并因此降低疾病风险的提议一致。
The inflammatory disease human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM/TSP) occurs in only 1-2% of HTLV-I-infected individuals and is associated with a high provirus load of HTLV-I, We hypothesize that a person's risk of developing HAM/TSP depends upon the efficiency of their immune response to the virus, which differs between individuals because of polymorphism in genes that influence this response. Previously we showed that the possession of HLA-A*02 was associated with a lower risk of HAM/TSP, and with a lower provirus load in healthy carriers of HTLV-I. However, HLA-A*02 did not account for all the observed difference in the risk of HAM/TSP, Here we present evidence, in the same study population in Japan, that HLA-Cw*08 was also associated with disease protection (probability value, two-tailed test = 0.002) and with a lower proviral load in healthy carriers. Possession of the A*02 and/or Cw*08 genes prevented 36% of potential HAM/TSP cases. In contrast, HLA-B*5401 was associated with a higher susceptibility to HAM/TSP (probability value, two-tailed test = 0.0003) and with a higher provirus load in HAM/TSP patients. At a given provirus load, B*5401 appeared to increase the risk of disease. The fraction of HAM/TSP cases attributable to B*5401 was 17%, Furthermore, individuals who were heterozygous at all three HLA class I loci have a lower HTLV-I provirus load than those who were homozygous at one or more loci. These results are consistent with the proposal that a strong class I-restricted CTL response to HTLV-I reduces the proposal load and hence the risk of disease.