Reduced Risk of BK Polyomavirus Infection in HLA-B51 Positive Kidney Transplant Recipients

Background 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. Methods 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. Results While 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 recipients (9%), reduced the risk of viremia approximately five-fold (HR 0.18, 95% CI: 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. Conclusions 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. Authorship The author's specific contributions are as follows: HFW and MCWF initiated the study. HFW, ACMK, JWdF, JIR, FHJC and MCWF designed the study. HFW, CSdB, GWH and JIR collected the samples and gathered the data. CSdB performed the serological tests and the PCR assays. HFW analysed the data. EWvZ and GWH provided statistical support. HFW, ACMK, JWdF, JIR, FHJC, and MCWF interpreted the data. HFW and MCWF drafted the manuscript, and designed the figures and tables. All authors reviewed and approved the final report. Disclosure The authors declare no conflicts of interest Funding This study was supported by the Dutch Kidney Foundation, grant 13A1D302. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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