BK polyomavirus (BKPyV) often reactivates after kidney transplantation, causing BKPyV-associated nephropathy (BKPyVAN) in 1%-10% of cases with a potential detrimental effect on allograft survival. Kidney transplant recipients are regularly screened for BKPyV DNA in plasma. As this strategy may not always reduce the risk of BKPyVAN, other predictive markers are needed. To evaluate the role of pretransplant BKPyV-specific antibody, 210 kidney transplant recipients and 130 donors were screened for BKPyV DNA and BKPyV-specific antibodies. We found that the donor BKPyV immunoglobulin G (IgG) seroprevalence and antibody level were strongly associated with BKPyV-DNAemia and BKPyVAN, although multivariant analysis found the presence of anti-BKPyV-specific antibodies as a predictive factor only for BKPyV-DNAemia. The pretransplant recipient status had no effect on posttransplant BKPyV-DNAemia and BKVAN. BKPyV IgG levels remained stable in BKPyV-negative recipients during 1-year follow-up, while a considerable increase was observed in BKPyV-positive patients. The presence of anti-BKPyV-specific antibodies in kidney allograft donors is a good and reliable predictive marker for posttransplant BKPyV replication with relevance to risk stratification in transplant recipients.

Department of Genetics and Microbiology Faculty of Science Charles University Prague Czechia

Department of Nephrology Transplant Centre Institute for Clinical and Experimental Medicine Prague Czechia

National Reference Laboratory for Papillomaviruses and Polyomaviruses Institute of Hematology and Blood Transfusion Prague Czechia

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Hirsch HH, Randhawa PS. BK polyomavirus in solid organ transplantation-guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant (2019) 33(9):e13528. doi: 10.1111/ctr.13528 PubMed DOI

Hirsch HH, Suthanthiran M. The natural history, risk factors and outcomes of polyomavirus BK-associated nephropathy after renal transplantation. Nat Clin Pract Nephrol (2006) 2(5):240–1. doi: 10.1038/ncpneph0179 PubMed DOI

Binggeli S, Egli A, Schaub S, Binet I, Mayr M, Steiger J, et al. . Polyomavirus BK-specific cellular immune response to VP1 and large T-antigen in kidney transplant recipients. Am J Transplant (2007) 7(5):1131–9. doi: 10.1111/j.1600-6143.2007.01754.x PubMed DOI

Mueller K, Schachtner T, Sattler A, Meier S, Friedrich P, Trydzenskaya H, et al. . BK-VP3 as a new target of cellular immunity in BK virus infection. Transplantation (2011) 91(1):100–7. doi: 10.1097/TP.0b013e3181fe1335 PubMed DOI

Sood P, Senanayake S, Sujeet K, Medipalli R, Van-Why SK, Cronin DC, et al. . Donor and recipient BKV-specific IgG antibody and posttransplantation BKV infection: a prospective single-center study. Transplantation (2013) 95(6):896–902. doi: 10.1097/TP.0b013e318282ba83 PubMed DOI

Wunderink HF, van der Meijden E, van der Blij-de Brouwer CS, Mallat MJ, Haasnoot GW, van Zwet EW, et al. . Pretransplantation donor-recipient pair seroreactivity against BK polyomavirus predicts viremia and nephropathy after kidney transplantation. Am J Transplant (2017) 17(1):161–72. doi: 10.1111/ajt.13880 PubMed DOI

Knight RJ, Gaber LW, Patel SJ, DeVos JM, Moore LW, Gaber AO. Screening for BK viremia reduces but does not eliminate the risk of BK nephropathy. Transplantation (2013) 95(7):949–54. doi: 10.1097/TP.0b013e31828423cd PubMed DOI

Hoffman NG, Cook L, Atienza EE, Limaye AP, Jerome KR. Marked variability of BK virus load measurement using quantitative real-time PCR among commonly used assays. J Clin Microbiol (2008) 46(8):2671–80. doi: 10.1128/JCM.00258-08 PubMed DOI PMC

Sroller V, Hamsikova E, Ludvikova V, Vochozkova P, Kojzarova M, Fraiberk M, et al. . Seroprevalence rates of BKV, JCV, and MCPyV polyomaviruses in the general Czech republic population. J Med Virol (2014) 86(9):1560–8. doi: 10.1002/jmv.23841 PubMed DOI

Hrbacek J, Urban M, Hamsikova E, Tachezy R, Eis V, Brabec M, et al. . Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients: a case-control study. BMC Cancer (2011) 11:53. doi: 10.1186/1471-2407-11-53.:53-11 PubMed DOI PMC

Ginevri F, de SR, Comoli P, Pastorino N, Rossi C, Botti G, et al. . Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches. Transplantation (2003) 75(8):1266–70. doi: 10.1097/01.TP.0000061767.32870.72 PubMed DOI

Smith JM, McDonald RA, Finn LS, Healey PJ, Davis CL, Limaye AP. Polyomavirus nephropathy in pediatric kidney transplant recipients. Am J Transplant (2004) 4(12):2109–17. doi: 10.1111/j.1600-6143.2004.00629.x PubMed DOI

Bohl DL, Storch GA, Ryschkewitsch C, Gaudreault-Keener M, Schnitzler MA, Major EO, et al. . Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia. Am J Transplant (2005) 5(9):2213–21. doi: 10.1111/j.1600-6143.2005.01000.x PubMed DOI

Bohl DL, Brennan DC, Ryschkewitsch C, Gaudreault-Keener M, Major EO, Storch GA. BK virus antibody titers and intensity of infections after renal transplantation. J Clin Virol (2008) 43(2):184–9. doi: 10.1016/j.jcv.2008.06.009 PubMed DOI PMC

Randhawa P, Bohl D, Brennan D, Ruppert K, Ramaswami B, Storch G, et al. . Longitudinal analysis of levels of immunoglobulins against BK virus capsid proteins in kidney transplant recipients. Clin Vaccine Immunol (2008) 15(10):1564–71. doi: 10.1128/CVI.00206-08 PubMed DOI PMC

Pastrana DV, Brennan DC, Cuburu N, Storch GA, Viscidi RP, Randhawa PS, et al. . Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. PloS Pathog (2012) 8(4):e1002650. doi: 10.1371/journal.ppat.1002650 PubMed DOI PMC

Randhawa P, Pastrana DV, Zeng G, Huang Y, Shapiro R, Sood P, et al. . Commercially available immunoglobulins contain virus neutralizing antibodies against all major genotypes of polyomavirus BK. Am J Transplant (2015) 15(4):1014–20. doi: 10.1111/ajt.13083 PubMed DOI PMC

Benotmane I, Solis M, Velay A, Cognard N, Olagne J, Gautier VG, et al. . Intravenous immunoglobulin as a preventive strategy against BK virus viremia and BKV-associated nephropathy in kidney transplant recipients-results from a proof-of-concept study. Am J Transplant (2021) 21(1):329–37. doi: 10.1111/ajt.16233 PubMed DOI

Wunderink HF, van der Meijden E, van der Blij-de Brouwer CS, Zaaijer HL, Kroes AC, van Zwet EW, et al. . Stability of BK polyomavirus IgG seroreactivity and its correlation with preceding viremia. J Clin Virol (2017) 90:46–51. doi: 10.1016/j.jcv.2017.03.015 PubMed DOI

Wunderink HF, de Brouwer CS, van der Meijden E, Pastrana DV, Kroes ACM, Buck CB, et al. . Development and evaluation of a BK polyomavirus serotyping assay using luminex technology. J Clin Virol (2019) 110:22–8. doi: 10.1016/j.jcv.2018.11.009 PubMed DOI PMC

Dakroub F, Touzé© A, Abdel SF, Fiore T, Morel V, Tinez C, et al. . The impact of pre-graft serology on the risk of BKPyV infection post-renal transplantation. Nephrol Dial Transplant (2021) 37:781–8. doi: 10.1093/ndt/gfab279 PubMed DOI

Nickeleit V, Singh HK, Dadhania D, Cornea V, El-Husseini A, Castellanos A, et al. . The 2018 banff working group classification of definitive polyomavirus nephropathy: A multicenter validation study in the modern era. Am J Transplant (2021) 21(2):669–80. doi: 10.1111/ajt.16189 PubMed DOI PMC

Hariharan S, Cohen EP, Vasudev B, Orentas R, Viscidi RP, Kakela J, et al. . BK virus-specific antibodies and BKV DNA in renal transplant recipients with BKV nephritis. Am J Transplant (2005) 5(11):2719–24. doi: 10.1111/j.1600-6143.2005.01080.x PubMed DOI

Ginevri F, Azzi A, Hirsch HH, Basso S, Fontana I, Cioni M, et al. . Prospective monitoring of polyomavirus BK replication and impact of pre-emptive intervention in pediatric kidney recipients. Am J Transplant (2007) 7(12):2727–35. doi: 10.1111/j.1600-6143.2007.01984.x PubMed DOI

Girmanova E, Brabcova I, Bandur S, Hribova P, Skibova J, Viklicky O. A prospective longitudinal study of BK virus infection in 120 Czech renal transplant recipients. J Med Virol (2011) 83(8):1395–400. doi: 10.1002/jmv.22106 PubMed DOI