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

Wunderink, Herman F., MD1; Haasnoot, Geert W.2; de Brouwer, Caroline S.1; van Zwet, Erik W., PhD3; Kroes, Aloysius C. M.1; de Fijter, Johan W.4; Rotmans, Joris I., MD4; Claas, Frans H. J.2; Feltkamp, Mariet C. W., MD1

doi: 10.1097/TP.0000000000002376
Original Clinical Science—General
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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. 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.

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.

1Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.

2Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.

3Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.

4Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.

Received 20 March 2018. Revision received 19 June 2018.

Accepted 21 June 2018.

The authors declare no conflicts of interest.

This study was supported by the Dutch Kidney Foundation, grant 13A1D302.

H.F.W. and M.C.W.F. initiated the study. H.F.W., A.C.M.K., J.W.dF., J.I.R., F.H.J.C., and M.C.W.F. designed the study. H.F.W., C.S.dB., G.W.H., and J.I.R. collected the samples and gathered the data. C.S.dB. performed the serological tests and the PCR assays. H.F.W. analyzed the data. E.W.vZ. and G.W.H. provided statistical support. H.F.W., A.C.M.K., J.W.dF., J.I.R., F.H.J.C., and M.C.W.F. interpreted the data. H.F.W. and M.C.W.F. drafted the manuscript, and designed the figures and tables. All authors reviewed and approved the final report.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Herman F. Wunderink, MD, Department of Medical Microbiology, University Medical Center Utrecht, Room G.04.5.13, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. (H.F.Wunderink@umcutrecht.nl).

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