HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma
HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma
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DOI：
10.1073/pnas.0915054107
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发表时间：
2010-04-06
影响因子：
11.1
通讯作者：
Jarrett, Ruth F.
中科院分区：
文献类型：
--
作者：
Hjalgrim, Henrik;Rostgaard, Klaus;Jarrett, Ruth F.
部分经典霍奇金淋巴瘤 (HL) 被认为与普遍存在的嗜淋巴细胞 EBV 感染有因果关系。 EBV 相关 HL 发生的决定因素仍知之甚少，但可能涉及病毒感染的免疫控制。因此，HLA I 类区域的标志物与 EBV 相关 HL 的风险相关。为了进一步研究 EBV 相关 HL 的宿主遗传成分，我们在包括 278 例 EBV 相关和 656 例 EBV 无关 HL 病例的病例系列分析中，在传染性单核细胞增多症 (IM)（EBV 相关 HL 的危险因素）的背景下同时研究了淋巴瘤与 HLA-A*01 和 HLA-A*02 的关联。通过逻辑回归，HLA-A*01 等位基因[每个等位基因的比值比 (OR)，2.15； [95% CI, 1.60-2.88] 与 HLA-A*02 等位基因增加相关（每个等位基因的 OR，0.70；95% CI，0.51-0.97），且 EBV 相关 HL 风险降低。这些等位基因特异性关联对应于 HLA-A*01 和 HLA-A*02 纯合子之间 EBV 相关 HL 风险的近 10 倍变异。 IM 病史也与 EBV 相关 HL 的风险相关（OR，3.40；95% CI，1.74-6.66）。在 HLA-A*02 存在的情况下，未发现 IM 病史与 EBV 相关 HL 之间的关联，因为该等位基因似乎中和了 IM 对 EBV 相关 HL 风险的影响。我们的研究结果表明，HLA I 类限制性 EBV 特异性细胞毒性 T 细胞反应和 IM 中 EBV 感染早期免疫反应中的事件在 EBV 相关 HL 的发病机制中发挥着关键作用。
A proportion of classical Hodgkin lymphoma (HL) is believed to be causally related to infection with the ubiquitous lymphotropic EBV. The determining factors for development of EBV-related HL remain poorly understood, but likely involve immunological control of the viral infection. Accordingly, markers of the HLA class I region have been associated with risk of EBV-related HL. To study the host genetic component of EBV-related HL further, we investigated the lymphoma's association with HLA-A*01 and HLA-A*02 simultaneously in the setting of infectious mononucleosis (IM), a risk factor for EBV-related HL, in a case-series analysis including 278 EBV-related and 656 EBV-unrelated cases of HL. By logistic regression, HLA-A*01 alleles [odds ratio (OR) per allele, 2.15; 95% CI, 1.60-2.88] were associated with increased and HLA-A*02 alleles (OR per allele, 0.70; 95% CI, 0.51-0.97) with decreased risk of EBV-related HL. These allele-specific associations corresponded to nearly 10-fold variation in risk of EBV-related HL between HLA-A*01 and HLA-A*02 homozygotes. History of IM was also associated with risk of EBV-related HL (OR, 3.40; 95% CI, 1.74-6.66). The association between history of IM and EBV- related HL was not seen in the presence of HLA-A*02 because this allele appeared to neutralize the effect of IM on EBV- related HL risk. Our findings suggest that HLA class I-restricted EBV-specific cytotoxic T-cell responses and events in the early immune response to EBV infection in IM play critical roles in the pathogenesis of EBV-related HL.