Prevalence of antibodies against BKPyV subtype I and IV in kidney transplant recipients and in the general Czech population

Abstract

Active infection with BK polyomavirus (BKPyV) may cause serious complications in transplantation settings. Recently, the level of BKPyV IgG seroreactivity in graft donors has been shown to predict viremia and BKPyV‐associated nephropathy in kidney transplant (KTx) recipients. Pretransplantation testing of the donor and recipient BKPyV serostatus could, therefore, identify patients at high risk. For the development of serological immunoassays, antibody response to the predominant BKPyV subtypes (BKPyV‐I and BKPyV‐IV) was studied using virus‐like particle (VLP)‐based enzyme‐linked immunosorbent assay (ELISA). VLPs made from the capsid protein, VP1, derived from BKPyV‐I and BKPyV‐IV subtypes were produced using a baculovirus expression system and used as antigens. The tests were used for IgG antibody determination in 50 KTx recipients and 111 healthy blood donors. While 87% of samples reacted with mixed BKPyV‐I and BKPyV‐IV antigens, only 49% of samples were reactive in both ELISA tests when using BKPyV‐I or BKPyV‐IV antigens separately. Twenty‐seven percent of healthy blood donors and 26% of KTx recipients were reactive only with BKPyV‐I, while 9% and 20% were reactive only with BKPyV‐IV, respectively. To determine the specificities of the antigens, selected seropositive samples were retested after preadsorption with soluble BKPyV‐I, BKPyV‐IV, or JC polyomavirus antigens. The experiments confirmed that recombinant VP1 VLP‐based ELISAs predominantly detected BKPyV type‐specific antibodies. The results imply that anti‐BKPyV antibody ELISA tests should contain a mixture of subtype‐specific VLP‐based antigens instead of antigen derived from the most prevalent BKPyV‐I subtype. The tests can be used for serological surveys of BKPyV infection and improved KTx patient management.

Nephrotoxicity of calcineurin inhibitors as a risk factor for BK polyomavirus replication after kidney transplantation

“…17,18 Higher titer of anti-BKPyV IgG in the donor and its lower titer in the recipient increase the probability of early BKPyV viremia. 19,20 We believe that with a high prevalence of BKPyV infection in the population, where more than 90% of adults become seropositive by the end of their twenty-third year, 21 we can expect similar anti-BKPyV antibodies distribution in our monitored groups.…”

“…Not only donor serostatus but also different BKPyV specific antibody titers, which may reflect current BKPyV replication, affect the risk of BKPyV viremia and viruria in renal recipients 17,18 . Higher titer of anti‐BKPyV IgG in the donor and its lower titer in the recipient increase the probability of early BKPyV viremia 19,20 . We believe that with a high prevalence of BKPyV infection in the population, where more than 90% of adults become seropositive by the end of their twenty‐third year, 21 we can expect similar anti‐BKPyV antibodies distribution in our monitored groups.…”

Serologic response to COVID-19 infection or vaccination in pediatric kidney transplant recipients compared to healthy children

“…Flower et al reported elevated BK specific IgM antibody levels that persisted for a long duration in post-transplantation adult KTR, compared to healthy controls [ 27 ]. On the other hand, Hejtmánková et al showed lower seroconversion rates following BK virus infection in KTR, compared to healthy controls (38% vs. 52%) [ 28 ]. Hence, it is difficult to discern whether the serologic response of our cohort to COVID-19 infection is comparable to responses of other common viral infections.…”

Precursors of Viral Proteases as Distinct Drug Targets

“…The polyprotein strategy is employed by positive RNA viruses, including retroviruses such as HIV (Human Immunodeficiency Virus) [ 17 ]; coronaviruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [ 20 ]; and by some DNA viruses, e.g., poxviruses (smallpox virus) [ 21 ] or herpesviruses [ 22 ]. Other DNA viruses, such as polyomaviruses [ 23 , 24 ], all negative RNA viruses (among them, influenza virus [ 25 ]), and double-stranded RNA viruses [ 26 ] use different strategies of protein expression and encode no protease.…”