Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Transplantation. 2019 Mar;103(3):604-612. doi: 10.1097/TP.0000000000002376.
Identification of specific HLA alleles and T-cell epitopes that influence the course of BK polyomavirus (BKPyV) infection after kidney transplantation (KTx), including development of BKPyV-associated nephropathy (BKPyVAN), can be useful for patient risk stratification and possibly vaccine development.
In a retrospective cohort of 407 living kidney donor-recipient pairs, donor and recipient HLA class I and II status were correlated with the occurrence of recipient BKPyV viremia and BKPyVAN in the first year after KTx. Relevant HLA alleles were systematically analyzed for candidate peptide epitopes in silico.
Although none of the 78 HLA alleles analyzed increased the risk of BKPyV viremia and BKPyVAN, a considerable reduction of BKPyV viremia and BKPyVAN cases was observed in HLA-B51-positive KTx recipients. Multivariate analysis showed that HLA-B51 positivity, found in 36 (9%) recipients, reduced the risk of viremia approximately fivefold (hazard ratio, 0.18; 95% confidence interval, 0.04-0.73; P = 0.017). Four HLA-B51-restricted putative cytotoxic T lymphocyte epitopes were identified, including a previously described HLA-B supermotif-containing peptide (LPLMRKAYL), encoded by 2 relevant T-antigens (small T and large T) and previously shown to be highly immunogenic.
In conclusion, HLA-B51-positive kidney transplant recipients were less susceptible to BKPyV infection, which might be explained by efficient presentation of a particular BKPyV-derived immunogenic peptide.
鉴定影响肾移植（KTx）后 BK 多瘤病毒（BKPyV）感染过程的特定 HLA 等位基因和 T 细胞表位，包括 BKPyV 相关肾病（BKPyVAN）的发展，可用于患者风险分层和可能的疫苗开发。
在 407 对活体供肾受者队列的回顾性研究中，将供者和受者 HLA I 类和 II 类的状态与 KTx 后第一年受者 BKPyV 血症和 BKPyVAN 的发生相关联。对相关 HLA 等位基因进行系统的分析，以确定候选肽表位。
虽然分析的 78 个 HLA 等位基因均未增加 BKPyV 血症和 BKPyVAN 的风险，但在 HLA-B51 阳性的 KTx 受者中，BKPyV 血症和 BKPyVAN 的病例明显减少。多变量分析表明，HLA-B51 阳性（在 36 例（9%）受者中发现）使病毒血症的风险降低约五倍（危险比，0.18；95%置信区间，0.04-0.73；P = 0.017）。鉴定了 4 个 HLA-B51 限制性潜在细胞毒性 T 淋巴细胞表位，包括先前描述的 HLA-B 超基序肽（LPLMRKAYL），由 2 个相关 T 抗原（小 T 和大 T）编码，先前已证明其具有高度免疫原性。
总之，HLA-B51 阳性的肾移植受者不易感染 BKPyV，这可能是由于有效呈现了一种特定的 BKPyV 衍生的免疫原性肽。
