Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Immun Inflamm Dis. 2022 Jul;10(7):e666. doi: 10.1002/iid3.666.
Although most adults are infected by Epstein-Barr virus (EBV), some patients develop highly lethal diseases associated with EBV infection, including EBV-hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV infections (CAEBV), and lymphoma, the pathogeneses of which remain to be investigated. The human leukocyte antigen (HLA) complex may be associated with the viral infection pathway, and, therefore, HLA alleles may be associated with EBV-related diseases and subpopulations of infected cells, studies related to EBV-associated diseases, and subpopulations of infected cells that were conducted in China are scarce.
In this study, we analyzed the high-resolution HLA genotypes of 269 patients with EBV-associated diseases and 213 EBV-seronegative hematopoietic stem cell donors using PCR-SBT assay and elucidated the associations of HLA-A, -B, -C, -DRB1, and -DQB1 alleles with EBV-associated diseases in the Chinese population, Benjamini-Hochberg correction to adjust for multiple testing. HLA genotypes were also analyzed in patients with EBV-associated diseases showing EBV-infected lymphocyte subpopulations.
We found that individuals carrying the following alleles showed the following levels of risks: HLA-DRB111 allele, reduced risk of EBV-related disease (OR [odds ratio]: 0.56; 95% confidence interval [95% CI]: 0.32-0.99; p < .05; Adjust p = .71); HLA-DQB106:02 allele, reduced risk (OR: 0.5699; 95% CI: 0.3486-0.9317; p < .05; Adjust p = .57); and HLA-B15:01 allele, increased risk (OR: 1.763; 95% CI: 0.3486-0.9317; p < .05; Adjust p = .57). Patients with EBV-associated diseases showing the B15:01 genotype had a higher risk of T-cell, NK-cell, and multicell infections than those with other genotype subgroups.
These findings highlight the importance of HLA genotype for assessing EBV infectivity.
虽然大多数成年人都被 EBV（Epstein-Barr virus）感染，但一些患者会发展出与 EBV 感染相关的高致死性疾病，包括 EBV 噬血细胞性淋巴组织细胞增生症（EBV-HLH）、慢性活动性 EBV 感染（CAEBV）和淋巴瘤，其发病机制仍有待研究。人类白细胞抗原（HLA）复合体可能与病毒感染途径有关，因此 HLA 等位基因可能与 EBV 相关疾病和受感染细胞亚群有关，在中国开展的与 EBV 相关疾病和受感染细胞亚群相关的研究很少。
本研究采用 PCR-SBT 法分析了 269 例 EBV 相关疾病患者和 213 例 EBV 血清阴性造血干细胞供者的高分辨率 HLA 基因型，并阐明了 HLA-A、-B、-C、-DRB1 和 -DQB1 等位基因与中国人 EBV 相关疾病的关联，采用 Benjamini-Hochberg 校正进行多重检验调整。还分析了 EBV 相关疾病患者中 EBV 感染淋巴细胞亚群的 HLA 基因型。
我们发现携带以下等位基因的个体具有以下风险水平：HLA-DRB111 等位基因，降低 EBV 相关疾病的风险（OR [比值比]：0.56；95%置信区间 [95%CI]：0.32-0.99；p<.05；调整后 p=0.71）；HLA-DQB106:02 等位基因，降低风险（OR：0.5699；95%CI：0.3486-0.9317；p<.05；调整后 p=0.57）；HLA-B15:01 等位基因，增加风险（OR：1.763；95%CI：0.3486-0.9317；p<.05；调整后 p=0.57）。携带 EBV 相关疾病且具有 B15:01 基因型的患者比具有其他基因型亚组的患者更有可能发生 T 细胞、NK 细胞和多细胞感染。
这些发现强调了 HLA 基因型在评估 EBV 感染性方面的重要性。
