Pre- and Post-Transplant Anti-BKV IgG Responses and HLA Associations in BK Virus Reactivation Among Renal Transplant Recipients
1
Department of Clinical Laboratory Sciences, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
2
Institute of Infection & Global Health, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool L69 7BE, UK
*
Author to whom correspondence should be addressed.
Immuno 2025, 5(2), 16; https://doi.org/10.3390/immuno5020016
Submission received: 24 February 2025
/
Revised: 26 April 2025
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Accepted: 30 April 2025
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Published: 9 May 2025
Abstract
BK virus (BKV) reactivation is a significant complication in renal transplant recipients, often leading to BK viremia and BK virus-associated nephropathy (BKVAN), which can compromise graft survival. While the routine monitoring of BKV DNA in blood aids in early detection, identifying pre-transplant risk factors remains a challenge. This study investigates the role of pre- and post-transplant anti-BKV IgG levels and human leukocyte antigen (HLA) alleles in predicting BKV reactivation. The hospital-based cross-sectional study was conducted on 38 renal transplant recipients, stratified into viremic, non-viremic, and BKVAN groups. Anti-BKV IgG levels were measured pre-transplant, at viremia onset, and post-viremia using ELISA. BKV DNA was detected via qPCR, and HLA typing was performed using sequence-specific oligonucleotide probe (SSOP) hybridization. Statistical analyses included Kaplan–Meier survival curves and Cox regression models. Pre-transplant anti-BKV IgG seropositivity was higher in viremic (94%) and BKVAN (100%) patients than in non-viremic recipients (66.6%). Post-transplant IgG levels increased significantly in viremic recipients (p < 0.05). HLA-B44 and HLA-DR15 were significantly associated with increased BKV viremia risk (p = 0.02 and p = 0.01, respectively). Pre-transplant anti-BKV IgG levels and specific HLA alleles influence BKV reactivation risk. These findings highlight the potential for integrating serological and genetic screening into pre-transplant assessments to improve risk stratification and post-transplant monitoring strategies.
1. Introduction
The introduction of immunosuppressive therapy in renal transplant recipients is essential to prevent allograft rejection but simultaneously creates an environment conducive to viral reactivation [1,2]. BK virus (BKV) reactivation occurs following kidney transplantation and can manifest as viruria in 30% to 40% or viremia in 10% to 20% [3]. The presence of BKV DNA in blood is particularly concerning, as it signals active viral replication, with 1–10% of viremic patients progressing to BK virus-associated nephropathy (BKVAN), a condition characterized by direct viral cytopathic effects and immune-mediated damage to the renal allograft [3,4]. The most effective strategy for managing BKVAN remains early detection through the routine screening of BKV DNA in blood, combined with reductions in immunosuppressive therapy upon the detection of viremia [5,6]. However, this approach is reactive rather than preventive, and significant effort has been directed toward identifying pre-transplant biomarkers that can predict post-transplant BKV reactivation [7,8,9]. A notable example is the BKV microRNA [10].
Pre-transplant anti-BKV IgG levels and recipient human leukocyte antigen (HLA) genotypes have emerged as promising candidates for risk assessment. Several studies have suggested an association between pre-transplant anti-BKV sero-status and the recipient’s infection status [11,12,13,14]. However, the risk of high or low pre-transplant anti-BKV levels (titers) has not been clearly determined [13,15]. Beyond humoral immunity, genetic factors also influence BKV reactivation risk. The HLA system plays a crucial role in antigen presentation and adaptive immune responses, and variations in HLA alleles may affect the ability of transplant recipients to mount effective immune responses against BKV [16]. Several studies have suggested associations between specific HLA alleles and BKV susceptibility, but certain alleles may be less efficient at presenting BKV antigens to cytotoxic T cells, thereby impairing viral clearance [17,18,19]. This study aimed to evaluate the association between pre- and post-transplant anti-BKV IgG levels, the development of BK viremia, and the potential influence of human leukocyte antigen (HLA) alleles on BKV susceptibility.
2. Materials and Methods
2.1. Study Design and Patient Recruitment
The study was a hospital-based cross-sectional study investigating BK virus (BKV) infection in renal transplant recipients. A total of 38 renal transplant recipients were enrolled from a single transplant center. Patients were recruited consecutively and provided informed consent before participation. Inclusion criteria required patients to be adults (≥18 years old) undergoing kidney transplantation. Exclusion criteria included patients with known immunodeficiency disorders, prior polyomavirus-related complications, or multiple organ transplants.
Clinical and demographic data were collected at baseline, including age, sex, underlying renal disease, type of immunosuppressive therapy, and history of previous graft rejection episodes. Participants were stratified into three groups based on post-transplant BK viral status: (1) patients who developed BK viremia (defined as ≥1000 copies/mL of BK viral DNA in blood), (2) patients who never developed BK viremia, and (3) patients who developed BKVAN.
2.2. Sample Collection and Storage
Blood samples were collected at three time points from each recipient:
- Pre-transplant: Blood samples were obtained before transplantation to assess baseline anti-BKV IgG levels and HLA typing.
- During viremia onset: In patients who developed BK viremia, additional blood samples were collected at the time of confirmed viremia detection.
- Post-transplant: A third sample was obtained at least one year post-transplant to evaluate long-term changes in anti-BKV IgG levels.
Blood samples were collected in serum-separating tubes (SSTs) and ethylenediaminetetraacetic acid (EDTA) tubes. Serum was separated by centrifugation at 3000 rpm for 10 min and stored at −80 °C until analysis. Whole-blood samples collected in EDTA tubes were used for BK viral DNA detection and HLA typing.
2.3. Laboratory Procedures
Detection of BK Virus DNA in Blood
BK viral DNA in blood samples was detected using the Artus BK Virus QS-RGQ Kit (QIAGEN, Hilden, Germany). Viral DNA extraction was performed using the QIAamp Viral DNA Mini Kit (Qiagen). The qPCR assay was set up in a 20 µL reaction mixture containing the provided PCR master mix, an internal control, and sample DNA. The kit contains primers and probes specifically amplifying a 274 bp region of the BKV VP2 and VP3 genes, covering all available BKV sequences, including rare strains of types II, III, and IV, and an artificial 280 bp internal control sequence that is co-amplified with the BKV DNA. The assay also included a specific TaqMan probe targeting a 274 bp region of the BK virus VP2 and VP3 genes, though the probe sequence is proprietary to the kit.
Standard quantification was achieved using the four BK virus quantitation standards supplied with the kit, allowing precise viral load determination. The qPCR conditions and cycling parameters followed the manufacturer’s guidelines. The viral load in blood samples was determined by comparing cycle threshold values to the standard curve, with results expressed as copies.
2.4. Enzyme-Linked Immunosorbent Assay (ELISA) for Anti-BKV IgG
A 100 µL aliquot of diluted plasma samples (1:100) was added to each well of the ELISA plate, which was pre-coated with a purified BK virus (BKV) VP1 capsid protein, the major immunogenic component of the virus and the primary antigen recognized by host antibodies. Wells were designated for positive and negative controls for validation. The plates were incubated at room temperature for one hour, followed by three washes with a wash buffer to remove unbound materials. Subsequently, 100 µL of an enzyme-linked secondary antibody (anti-human IgG conjugated to horseradish peroxidase, HRP) was added to each well and incubated for another hour at room temperature, followed by three additional washes. A 100 µL volume of substrate solution was then added to each well and incubated in the dark for 10–15 min. The reaction was terminated by adding a stop solution, and the optical density (OD) was measured at 450 nm using an ELISA plate reader. BKV IgG concentrations were determined by comparing the sample OD values with those of the controls.
2.5. HLA Typing
HLA typing was performed using a high-resolution sequence-specific oligonucleotide probe (SSOP) hybridization assay. DNA was extracted from whole blood using a genomic DNA extraction kit and amplified via polymerase chain reaction (PCR) using locus-specific primers targeting HLA-A, HLA-B, and HLA-DR alleles. Amplified DNA was hybridized to HLA-specific probes immobilized on a microarray platform. The hybridization pattern was analyzed using an automated system, and allele assignments were made based on fluorescence intensity comparisons to a reference database. High-resolution typing allowed for the precise identification of HLA class I (HLA-A and HLA-B) and class II (HLA-DR) alleles.
2.6. Statistical Analysis
Data were analyzed using GraphPad prism 8. Continuous variables were expressed as mean ± standard deviation (SD) and compared using Student’s t-test or one-way ANOVA as appropriate. Categorical variables were analyzed using the chi-square or Fisher’s exact test. Kaplan–Meier survival curves were generated to assess the risk of BKV viremia in relation to HLA allele status, and differences between groups were analyzed using the log-rank test. Multivariate Cox regression analysis was performed to identify independent risk factors associated with BK viremia, with hazard ratios (HR) and 95% confidence intervals (CI) reported. A p-value of < 0.05 was considered statistically significant.
2.7. Ethical Considerations
The University of Liverpool’s Interventional Ethics Committee granted ethical approval for the study. Informed consent was obtained from all participants in accordance with ethical standards for human research and the principles outlined in the Helsinki Declaration of 1975, as revised in 2000. This process was conducted through the completion of informed consent forms by all participants.
3. Results
3.1. Patient Demographics and Clinical Characteristics
A total of 38 renal transplant recipients were included in this study, with follow-up data collected over a post-transplantation period. Among these recipients, 18 (47.0%) developed BK viremia after transplantation, exhibiting an average viral load of 5.3 × 103 copies/mL, with peak viremia levels reaching up to 10 × 104 copies/mL within the first year of transplantation. Meanwhile, 15 patients (39.4%) did not develop detectable BK viremia throughout the follow-up period, and 5 (13.0%) exhibited sustained low viral loads that did not progress to significant viremia. Among the viremic group, three recipients (16.6%) developed BK virus-associated nephropathy (BKVAN). Additionally, six cases of acute graft rejection were documented in the study population. Notably, half of these rejection episodes were associated with complications of BKVAN, while the other half were linked to unrelated causes. A comparative analysis of demographic and clinical characteristics between the study groups revealed no significant differences in key variables, including patient age, underlying diseases, sex distribution, or immunosuppressive therapy regimens (Table 1).
3.2. Pre- and Post-Transplant Anti-BKV IgG Levels
To assess prior BK virus exposure and the immunological response post-transplantation, anti-BKV IgG antibody levels were measured in all recipients using a sandwich ELISA. This allowed for a quantitative comparison of antibody responses before and after transplantation. Pre-transplant anti-BKV IgG seropositivity varied among the study groups. In recipients who never developed BK viremia, 66.6% tested positive for anti-BKV IgG, while a higher proportion (94.0%) of those who developed BK viremia exhibited pre-transplant seropositivity. All of the recipients who progressed to BKVAN were positive for anti-BKV IgG before transplantation (Table 2). A comparison of mean pre-transplant antibody levels showed a notable trend. Recipients who subsequently developed BK viremia had lower pre-transplant anti-BKV IgG levels (6.87 ± 0.32) compared to those who remained viremia-free (7.704 ± 0.31). Meanwhile, patients who progressed to BKVAN had a mean pre-transplant IgG level of 7.5 ± 0.94 (p = 0.14) (Figure 1). Post-transplantation, there was a marked increase in anti-BKV IgG levels in viremic recipients (10.21 ± 0.5) compared to those who never had viremia (4.627 ± 2.9). A similar trend was observed in BKVAN patients, where the mean post-transplant IgG level was significantly elevated (10.50 ± 0.23) (p < 0.05) compared to the non-viremic group (Figure 2).
3.3. Longitudinal Changes in Anti-BKV IgG Levels
To further investigate immune responses over time, anti-BKV IgG levels were measured at three key time points in recipients who developed BK viremia: pre-transplant, at the onset of viremia, and after clearance of viremia. In recipients who developed viremia, mean pre-transplant anti-BKV IgG levels were 6.24 ± 0.45. A significant increase in antibody levels was observed at the onset of BK viremia, rising to 9.42 ± 0.67 (p < 0.00001). Following virus clearance, IgG levels remained elevated at 10.21 ± 0.53, with no significant decline after viremia resolution (p = 0.8) (Figure 3A). In contrast, recipients who remained free of BK viremia did not exhibit significant fluctuations in their anti-BKV IgG levels over time. The mean antibody levels in this group were 4.98 ± 2.70 pre-transplant and remained stable at 4.62 ± 2.90 one-year post-transplantation (p = 0.77) (Figure 3B).
3.4. Association Between HLA Alleles and BK Viremia
To determine whether specific human leukocyte antigen (HLA) alleles influence susceptibility to BK viremia, HLA-A, HLA-B, and HLA-DR allele frequencies were analyzed in recipients with and without viremia. Certain HLA alleles were found to be more frequent in recipients who developed viremia. These included HLA-B44 and HLA-DR15, which were significantly associated with an increased risk of BK viremia (Table 3). Conversely, alleles such as HLA-B8 and HLA-DR13 were more frequently detected in recipients who never developed viremia, though the differences were not statistically significant. A total of 17 recipients tested positive for HLA-B44, of whom 14 (82%) developed viremia, compared to 3 non-viremic individuals (p = 0.02). Similarly, 11 out of 12 recipients positive for HLA-DR15 (91%) developed BK viremia, whereas only 1 recipient without viremia had this allele (p = 0.01). Kaplan–Meier survival analysis further confirmed the association between these alleles and BK viremia risk. Recipients with HLA-B44 and HLA-DR15 exhibited significantly higher cumulative incidence rates of BK viremia over the two-year follow-up period (p = 0.001 and p = 0.02, respectively) (Figure 4 and Figure 5).
3.5. Multivariate Analysis of Risk Factors for BK Viremia
To assess independent predictors of BK viremia, a multivariate Cox regression model was constructed, incorporating key clinical and immunological variables (Table 4). HLA-B44 (HR: 0.296, 95% CI: 0.11–0.73, p = 0.009) and HLA-DR15 (HR: 0.44, 95% CI: 0.18–1.08, p = 0.07) were identified as significant predictors of viremia. The male gender also showed a trend toward increased risk (HR: 0.4, 95% CI: 0.63–1.12, p = 0.08), though it did not reach statistical significance. In contrast, other variables such as HLA-A2 status and the overall HLA mismatch were not significantly associated with viremia development.
4. Discussion
BK virus (BKV) reactivation in renal transplant recipients remains a critical challenge in post-transplant management, with significant implications for graft survival and patient outcomes [4]. In this study, we investigated the relationship between pre-transplant anti-BKV IgG levels, post-transplant antibody responses, and the role of specific human leukocyte antigen (HLA) alleles in the development of BKV viremia and nephropathy.
The findings of this study revealed that pre-transplant anti-BKV IgG seropositivity was higher in recipients who later developed BKV viremia compared to those who remained viremia-free. Also, while the mean pre-transplant anti-BKV IgG levels were slightly lower in recipients who developed viremia compared to those who did not, this difference was not statistically significant. These findings align with the assumption that pre-existing anti-BKV antibodies may not necessarily confer protection against post-transplant viremia [15]. Saláková et al. (2022) similarly observed that pre-transplant seropositivity was common in renal transplant recipients [14]. The slight reduction in pre-transplant IgG levels in viremic patients in our study may indicate an immune status that is less effective at suppressing latent BKV infection, which could lead to viral reactivation under immunosuppressive conditions. However, an alternative explanation worth considering is that the post-transplant increase in antibody titers in viremic individuals may reflect a new infection rather than the reactivation of a latent virus. This could be due to donor-derived viral transmission, especially in cases where the recipient’s pre-existing antibodies are not fully cross-reactive with the donor’s BKV strain. However, some studies have suggested that high pre-transplant anti-BKV antibody levels may provide protection. For example, Solis et al. (2018) reported that patients with high neutralizing antibody (NAb) titers against the replicating BKV strain had a reduced risk of developing BKV viremia [20]. However, the protective role of pre-transplant BKV-specific antibodies in transplant recipients has long been considered insignificant [21]. Nonetheless, the findings of the study highlight the complexity of BKV immunity.
Following transplantation, a significant increase in anti-BKV IgG levels in recipients who developed viremia was observed, with mean post-transplant antibody levels rising higher than those of non-viremic recipients. This trend was even more pronounced in patients who progressed to BKVAN, where post-transplant IgG levels reached higher peaks. These findings suggest that BKV infection induces a strong humoral immune response, potentially as a compensatory mechanism in the absence of effective cellular immunity due to immunosuppressive therapy. This is consistent with the findings of Bohl et al. (2008), who demonstrated that the mean antibody level increased in accordance with the intensity of the infection post-transplant [22]. Similarly, Randhawa et al. (2008) found that post-transplant anti-BKV IgG levels increased in viremic patients, particularly in those who developed BKV nephropathy [23]. The sustained elevation of IgG levels even after viral clearance in our study further supports the notion that humoral immunity remains active against BKV long after the acute phase of infection has resolved.
However, while increased antibody levels correlate with viral replication, they do not necessarily prevent disease progression. This paradox may be explained by the inability of humoral immunity alone to control BKV replication in the absence of robust T-cell responses. Unlike other viral infections where neutralizing antibodies can clear the virus effectively, BKV reactivation appears to be more dependent on cell-mediated immunity, as demonstrated in studies showing that cell-mediated responses are crucial in controlling polyomavirus infections [24,25].
Our longitudinal analysis of anti-BKV IgG levels revealed that in viremic patients, antibody levels increased significantly from pre-transplant levels to the onset of viremia. After viral clearance, IgG levels remained elevated without a significant decline. This persistence of elevated antibody titers suggests that immune memory is retained post-viremia, which may provide some protection against future reactivation. However, in recipients who never developed viremia, anti-BKV IgG levels remained stable over time, with no significant difference between pre- and post-transplant antibody levels. This suggests that in the absence of viral replication, BKV-specific humoral immunity does not undergo significant stimulation post-transplantation. Similar findings were reported by Bohl et al. (2008), who noted that antibody titers remained relatively unchanged in non-viremic recipients [22].
A novel aspect of our study was the analysis of HLA allele distributions among transplant recipients and their association with BKV viremia. The findings of this study demonstrated that specific HLA alleles, particularly HLA-B44 and HLA-DR15, were significantly associated with an increased risk of viremia. Recipients carrying HLA-B44 had an 82% likelihood of developing BKV viremia (p = 0.02), while those with HLA-DR15 had a 91% likelihood of viremia (p = 0.01). In contrast, HLA-B8 and HLA-DR13 were more frequent in non-viremic recipients, though these associations were not statistically significant. These findings are in agreement with previous studies suggesting that certain HLA alleles may predispose individuals to BKV reactivation [17]. Teutsch et al. (2015) found that recipients with HLA-A28 and HLA-A68 had an increased risk of viremia, possibly due to weaker antigen presentation to T cells [26]. Similarly, Bohl et al. (2005) reported that the absence of HLA-C7 in donors was associated with a higher risk of sustained viremia, suggesting that HLA-mediated immune surveillance plays a critical role in controlling BKV replication [18].
The mechanisms underlying the association between HLA alleles and BKV susceptibility remain unclear, but it is hypothesized that certain HLA class I and II molecules may be less effective at presenting BKV antigens to CD8+ and CD4+ T cells, respectively [27]. This could lead to impaired cellular immunity and increased viral replication in individuals carrying these alleles. Alternatively, HLA mismatch-related rejection episodes may result in increased immunosuppressive therapy, further enhancing susceptibility to BKV reactivation [19].
In this study, the significance of anti-BKV antibody levels in assessing the risk of BKV reactivation is highlighted through their association with DNA viremia, which serves as a clear marker of active viral replication. Although high pre-transplant anti-BKV IgG seropositivity was observed in viremic and BKVAN patients compared to non-viremic recipients, this alone does not imply protective immunity. Instead, it may reflect prior exposure to the virus without sufficient immune control to prevent reactivation. The subsequent rise in antibody levels post-viremia suggests a secondary immune response triggered by active viral replication. Therefore, combining serological profiling with BKV DNA monitoring offers a more comprehensive and clinically meaningful approach to identifying individuals at greater risk of reactivation, particularly when supported by genetic markers such as specific HLA alleles.
5. Conclusions
The study provides valuable insights into the immunological factors associated with BKV viremia in renal transplant recipients. The findings demonstrated that pre-transplant anti-BKV IgG seropositivity is high in viremic patients but does not necessarily confer protection. Post-transplant, significant increases in antibody levels correlate with viremia, yet immune control remains incomplete in the absence of effective cellular immunity. Also, the study identified HLA-B44 and HLA-DR15 as potential genetic risk factors for BKV reactivation. There is a need for individualized risk assessment in renal transplantation. Further research into the immune-mediated mechanisms of BKV pathogenesis should also be explored.
Author Contributions
D.I.F.—conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, validation, visualization, writing—original draft, and writing—review and editing; S.C.—conceptualization, data curation, methodology, resources, supervision, visualization, and writing—original draft. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by Prince Sattam Bin Abdulaziz University (project number (PSAU/2024/R/1445)).
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the National Research Ethics Services North West (IRAS ID: 229214) for studies involving humans.
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
Data are available upon request.
Conflicts of Interest
The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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Figure 1.
Pre-transplant anti-BKV IgG levels in recipients with and without BK viremia. Antibodies in pre-transplant recipients who developed BKV viremia following transplant. One-way ANOVA test was used to compare the mean antibody titers between the groups (p = 0.14), N = 38.
Figure 1.
Pre-transplant anti-BKV IgG levels in recipients with and without BK viremia. Antibodies in pre-transplant recipients who developed BKV viremia following transplant. One-way ANOVA test was used to compare the mean antibody titers between the groups (p = 0.14), N = 38.
Figure 2.
Post-transplant anti-BKV IgG levels in recipients with and without BK viremia. Antibody levels in post-transplant recipients who developed BKV viremia after the transplant. One-way ANOVA test was used to compare the mean antibody titers between the groups (p < 0.05), N = 28.
Figure 2.
Post-transplant anti-BKV IgG levels in recipients with and without BK viremia. Antibody levels in post-transplant recipients who developed BKV viremia after the transplant. One-way ANOVA test was used to compare the mean antibody titers between the groups (p < 0.05), N = 28.
Figure 3.
(A) Longitudinal changes in anti-BKV IgG levels in recipients with BK viremia. (B) Anti-BKV IgG levels in non-viremic recipients. For the post-transplant BKV viremia group, the antibody was measured prior to the transplant, at the onset of the viremia, and after virus clearance; each box represents the interquartile range. p-value calculated using paired t-test. p < 0.05.
Figure 3.
(A) Longitudinal changes in anti-BKV IgG levels in recipients with BK viremia. (B) Anti-BKV IgG levels in non-viremic recipients. For the post-transplant BKV viremia group, the antibody was measured prior to the transplant, at the onset of the viremia, and after virus clearance; each box represents the interquartile range. p-value calculated using paired t-test. p < 0.05.
Figure 4.
Kaplan–Meier survival curve showing the risk of BK viremia in recipients with HLA-B44. The risk in the first two years post-transplantation based on HLA-B44 status. Kaplan–Meier survival curves were generated for 17 renal recipients with HLA-B44 and 20 without HLA-B44. Tick marks represent censored recipients. The p-value was calculated using a log-rank (Mantel–Cox) test. p-value < 0.05 was considered significant.
Figure 4.
Kaplan–Meier survival curve showing the risk of BK viremia in recipients with HLA-B44. The risk in the first two years post-transplantation based on HLA-B44 status. Kaplan–Meier survival curves were generated for 17 renal recipients with HLA-B44 and 20 without HLA-B44. Tick marks represent censored recipients. The p-value was calculated using a log-rank (Mantel–Cox) test. p-value < 0.05 was considered significant.
Figure 5.
Kaplan–Meier survival curve showing the risk of BK viremia in recipients with HLA-DR15. The risk in the first two years post-transplantation based on HLA-DR 15 status. Kaplan–Meier survival curves were generated for 13 renal recipients with HLA-DR15 and 24 without HLA-DR15. Tick marks represent censored recipients. The p-value was calculated using a long-rank (Mantel–Cox) test. p-value < 0.05 was considered significant.
Figure 5.
Kaplan–Meier survival curve showing the risk of BK viremia in recipients with HLA-DR15. The risk in the first two years post-transplantation based on HLA-DR 15 status. Kaplan–Meier survival curves were generated for 13 renal recipients with HLA-DR15 and 24 without HLA-DR15. Tick marks represent censored recipients. The p-value was calculated using a long-rank (Mantel–Cox) test. p-value < 0.05 was considered significant.
Table 1.
Clinical and demographic characteristics of renal transplant recipients with and without BK viremia.
Table 1.
Clinical and demographic characteristics of renal transplant recipients with and without BK viremia.
| Parameters | Recipients = 38 | Viremia = 18 | |||||
|---|---|---|---|---|---|---|---|
| Non-Viremia | Viremia | Low Viral Loads | p-Value | No BKVAN | BKVAN | p-Value (p < 0.05) | |
| No. patients (%) | 15 (39.5) | 18 (47.4) | 5 (13) | 15 (83.3) | 3 (16.6) | ||
| Patient’s sex (male) | 8 (53.3) | 12 (66.6) | 2 (40) | 0.2 | 10 (66.6) | 2 (66.6) | NS |
| Age (mean ±/− SD) | 58.17 ± 14.7 | 56 ± 13.7 | 59.6 ± 12.6 | 0.8 | 57 ± 11 | 46.6 ± 5 | NS |
| First → graft (%) | 11 (73.3) | 17 (100) | 4 (80) | NS | 15 (100) | 3 (100) | NS |
| Underlying condition (%) | |||||||
| Obstructive urology (%) | 3 (20) | 0 | 1 (20) | NS | NS | ||
| Hypertension (%) | 2 (13) | 6 (35) | 2 (40) | NS | 6 (40) | 0 | NS |
| Polycystic kidney (%) | 4 (26.6) | 1 (5.8) | 0 | NS | 1 (6.6) | 0 | NS |
| Other (%) | 6 (40.0) | 11 (58.8) | 2 | NS | 8 (60) | 3 | NS |
| Induction of Immune Suppression (%) | |||||||
| Campath | 70.9 | 71.5 | 40 | NS | 12 (80) | 3 (100) | |
| Simulect | 29.1 | 28.5 | 60 | NS | 3 (20) | 0 | |
| Maintenance suppression (%) | |||||||
| MMF + Advagraf | 4 (16) | 2 (28) | 1 (20) | NS | 1 (6.6) | 1 (30) | |
| Azathioprine | 4 (16) | 4 (22) | 0 | NS | 3 (20) | 1 (30) | |
| MMF + prograf | 3 (12.5) | 2 (11) | 1 (20) | NS | 2 (13) | 0 | |
| Advagraf (%) | 2 (8.3) | 2 (28) | 1 (20) | NS | 5 (30) | 1 (30) | |
| MMF | 6 (25) | 3 (42) | 2 (40) | NS | 3 (20) | 0 | |
| MMF + TAC (%) | 5 (20) | 1 (5) | 0 | 1 (6.6) | 0 | ||
| HLA mismatch mean ± SD | |||||||
| A | 0.88 ± 0.58 | 0.88 ± 0.78 | 1 ± 0.7 | NS | 0.92 ± 0.37 | 1 | |
| B | 0.77 ± 0.54 | 0.77 ± 0.83 | 0.4 ± 0.54 | NS | 0.84 ± 0.3 | 0.66 ± 0.033 | |
| DR | 0.66 ± 0.68 | 0.44 ± 0.72 | 0.6 ± 0.54 | NS | 0.92 ± 0.57 | 0.66 ± 33 | 0.4 |
| A + B + DR | 2.2 ± 1.4 | 2.1 ± 1.9 | 2.4 ± 1.5 | NS | 2.7 ± 1.9 | 2.3 ± 1.33 | |
| Acute rejection episode (%) | 3 (12.5) | 3 (16.6) | 1 (33) | ||||
| Post-operation period (months) | 3.5 | 10 | |||||
NS, no significant differences between the recipient groups. MMF, mycophenolate mofetil therapy. TAC, tacrolimus. The data are shown as mean ± standard deviation or percentage. The p-value was calculated using Student’s t test, one-way ANOVA, chi square, and Fisher’s exact test. p-value < 0.05 is considered significant.
Table 2.
Comparison of pre- and post-transplant anti-BKV IgG levels in renal transplant recipients.
| BKV Status | Pre-Transplant Seroprevalence (%) | Pre- Transplant Ab Titre | Post Operation > 1 Year | p- Value |
|---|---|---|---|---|
| Never BKV | 66.6 | 7.704 ± 0.31 | 4.627 ± 2.9 | 0.7 |
| BKV viremia | 94.4 | 6.87± 0.32 | 10.21 ± 0.5 | <0.05 |
| BVPyAN | 100 | 7.5 ± 0.94 | 10.50 ± 0.23 | <0.04 |
| p = 0.14 |
p-value was calculated using paired Student’s t test, and p-value < 0.05 was considered significant.
Table 3.
Frequency of HLA alleles in renal transplant recipients with and without BK viremia.
| BKV Viremia N = 23 (%) | No Viremia N = 15 (%) | p Value (p < 0.05) | |
|---|---|---|---|
| HLA-A1 (%) | 6 (26) | 6 (40) | 0.7 |
| A2 | 6 (26) | 5 (33) | 0.8 |
| HLA-B8 | 2 (8.6) | 5 (33) | 0.2 |
| B44 | 14 (60) | 3 (20) | 0.02 * |
| B51 | 1 (4.3) | 1 (6.6) | 1 |
| HLA-DR1 | 6 (26) | 2 (13) | 0.6 |
| DR3 | 2 (8.6) | 2 (13) | 1 |
| DR4 | 7 (30) | 2 (13) | 0.3 |
| DR7 | 2 (8.6) | 4 (26) | 0.37 |
| DR11 | 1 (4.3) | 2 (13) | 0.5 |
| DR13 | 1 (4.3) | 4 (26) | 0.15 |
| DR15 | 11 (47) | 1 (6.6) | 0.01 * |
All p-values correspond to the HLA in the corresponding row. p-value < 0.05 was considered significant.
Table 4.
Multivariate Cox regression analysis of risk factors for BK viremia.
| HR | 95% CI | p-Value | |
|---|---|---|---|
| Age | 0.46 | 0.009–0.15 | 0.6 |
| Gender | 0.42 | 0.63–1.12 | 0.08 |
| HLA-B44 | 0.296 | 0.11–0.73 | 0.009 |
| HLA-DR15 | 0.44 | 0.18–1.08 | 0.07 |
| HLA-A2 | 0.51–3.20 | 0.59 | |
| HLA-mismatch | 0.28 | ||
| A | 2.9 | 0.6–13.7 | 0.177 |
| B | 2.3 | 0.06–27 | 0.489 |
| DR | 0.18 | 0.22–1.5 | 0.115 |
p-value < 0.05 was considered significant.
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MDPI and ACS Style
Fallatah, D.I.; Christmas, S. Pre- and Post-Transplant Anti-BKV IgG Responses and HLA Associations in BK Virus Reactivation Among Renal Transplant Recipients. Immuno 2025, 5, 16. https://doi.org/10.3390/immuno5020016
AMA Style
Fallatah DI, Christmas S. Pre- and Post-Transplant Anti-BKV IgG Responses and HLA Associations in BK Virus Reactivation Among Renal Transplant Recipients. Immuno. 2025; 5(2):16. https://doi.org/10.3390/immuno5020016
Chicago/Turabian StyleFallatah, Deema Ibrahim, and Steve Christmas. 2025. "Pre- and Post-Transplant Anti-BKV IgG Responses and HLA Associations in BK Virus Reactivation Among Renal Transplant Recipients" Immuno 5, no. 2: 16. https://doi.org/10.3390/immuno5020016
APA StyleFallatah, D. I., & Christmas, S. (2025). Pre- and Post-Transplant Anti-BKV IgG Responses and HLA Associations in BK Virus Reactivation Among Renal Transplant Recipients. Immuno, 5(2), 16. https://doi.org/10.3390/immuno5020016
