Transplantation · 2019
Reduced Risk of BK Polyomavirus Infection in HLA-B51-positive Kidney Transplant Recipients.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wunderink Herman F, Haasnoot Geert W, de Brouwer Caroline S, van Zwet Erik W, Kroes Aloysius C M, de Fijter Johan W, Rotmans Joris I, Claas Frans H J, Feltkamp Mariet C W
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAgedAllelesBK VirusEpitopesFemaleGenotypeHLA-B51 AntigenHistocompatibility AntigensHumansKidney Failure, ChronicKidney TransplantationLiving DonorsMaleMiddle AgedMultivariate AnalysisPeptidesPolyomavirus InfectionsRetrospective StudiesRiskT-LymphocytesTransplant RecipientsTumor Virus InfectionsViremia