Human polyomavirus 9 infection in kidney transplant patients.
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ABSTRACT:
SUBMITTER: van der Meijden E
PROVIDER: S-EPMC4036759 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy.
| S-EPMC3325208 | biostudies-literature
Project description:Screening for polyomavirus infection after kidney transplantation is recommended by clinical practice guidelines, but cost-effectiveness of this strategy is uncertain. The aim of this study was to estimate the incremental costs and benefits of routine screening for polyomavirus infection compared with no screening in kidney transplant recipients.MethodsProbabilistic Markov models were constructed to compare the health and economic benefits of routine screening for polyomavirus infection using real-time polymerase chain reaction assay. A series of 1-way and probabilistic sensitivity analyses were conducted to define the most influential variables in the model.ResultsMonthly screening for 6 mo followed by 3 monthly screenings until 12 mo after transplant was dominant (lower costs and improved outcomes). Compared with no screening, the incremental benefits of screening were 0.294 life-years saved and 0.232 quality-adjusted life-years saved. Total savings from screening were $6986 Australian dollars ($5057 US dollars). The cost-effectiveness ratios were most sensitive to the costs of transplantation and dialysis, age of transplantation, prevalence of viremia, and probability of death in patients with a history of polyomavirus-associated nephropathy. Probabilistic sensitivity analysis indicated that screening (compared with no screening) was the dominant strategy across all plausible ranges of transition probabilities.ConclusionsScreening for polyomavirus infections 1 year following transplantation appears to save money, improves survival, and improves quality of life in kidney transplant recipients.
| S-EPMC9018998 | biostudies-literature
Project description:Background and objectivesBK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients.Design, setting, participants, & measurementsWe studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database.ResultsThe multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95).ConclusionsIn a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.
| S-EPMC8259491 | biostudies-literature
Project description:WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient's lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient.
| S-EPMC4696717 | biostudies-literature
Project description:BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation.
| S-EPMC5451008 | biostudies-literature
Project description:Nowadays, better immunosuppressors have decreased the rates of acute rejection in kidney transplantation, but have also led to the emergence of BKV-associated nephropathy (BKVAN). Therefore, we prospectively investigated BKV load in plasma and urine samples in a cohort of kidney transplants, receiving basiliximab combined with a mycophenolate mofetil-based triple immunotherapy, to evaluate the difference between BKV replication during the first 3 months post-transplantation, characterized by the non-depleting action of basiliximab, versus the second 3 months, in which the maintenance therapy acts alone. We also performed sequencing analysis to assess whether a particular BKV subtype/subgroup or transcriptional control region (TCR) variants were present.We monitored BK viruria and viremia by quantitative polymerase chain reaction (Q-PCR) at 12 hours (Tx), 1 (T1), 3 (T2) and 6 (T3) months post-transplantation among 60 kidney transplant patients. Sequencing analysis was performed by nested-PCR with specific primers for TCR and VP1 regions. Data were statistically analyzed using ?² test and Student's t-test.BKV was detected at Tx in 4/60 urine and in 16/60 plasma, with median viral loads of 3.70 log GEq/mL and 3.79 log GEq/mL, respectively, followed by a significant increase of both BKV-positive transplants (32/60) and median values of viruria (5.78 log GEq/mL) and viremia (4.52 log GEq/mL) at T2. Conversely, a significantly decrease of patients with viruria and viremia (17/60) was observed at T3, together with a reduction of the median urinary and plasma viral loads (4.09 log GEq/mL and 4.00 log GEq/mL, respectively). BKV TCR sequence analysis always showed the presence of archetypal sequences, with a few single-nucleotide substitutions and one nucleotide insertion that, interestingly, were all representative of the particular subtypes/subgroups we identified by VP1 sequencing analysis: I/b-2 and IV/c-2.Our results confirm previous studies indicating that BKV replication may occur during the early hours after kidney transplantation, reaches the highest incidence in the third post-transplantation month and then decreases within the sixth month, maybe due to induction therapy. Moreover, it might become clinically useful whether specific BKV subtypes or rearrangements could be linked to a particular disease state in order to detect them before BKVAN onset.
| S-EPMC3179958 | biostudies-literature
Project description:BackgroundA number of cerebral manifestations are associated with JC polyomavirus (JCPyV) which are diagnosed by detection of JCPyV in cerebrospinal fluid (CSF), often with the support of cerebral imaging. Here we present an unusual case of a kidney transplant patient presenting with progressive neurological deterioration attributed to JCPyV encephalopathy.MethodsQuantitative polymerase chain reaction JCPyV was used prospectively and retrospectively to track the viral load within the patient blood, urine, CSF, and kidney sections. A JCPyV VP1 enzyme-linked immunosorbent assay was used to measure patient and donor antibody titers. Immunohistochemical staining was used to identify active JCPyV infection within the kidney allograft.ResultsJC polyomavirus was detected in the CSF at the time of presentation. JC polyomavirus was not detected in pretransplant serum, however viral loads increased with time, peaking during the height of the neurological symptoms (1.5E copies/mL). No parenchymal brain lesions were evident on imaging, but transient cerebral venous sinus thrombosis was present. Progressive decline in neurological function necessitated immunotherapy cessation and allograft removal, which led to decreasing serum viral loads and resolution of neurological symptoms. JC polyomavirus was detected within the graft's collecting duct cells using quantitative polymerase chain reaction and immunohistochemical staining. The patient was JCPyV naive pretransplant, but showed high antibody titers during the neurological symptoms, with the IgM decrease paralleling the viral load after graft removal.ConclusionsWe report a case of atypical JCPyV encephalopathy associated with cerebral venous sinus thrombosis and disseminated primary JCPyV infection originating from the kidney allograft. Clinical improvement followed removal of the allograft and cessation of immunosuppression.
| S-EPMC5201453 | biostudies-literature
Project description: Not available
| S-EPMC2630759 | biostudies-literature
Project description:Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.
| S-EPMC7926448 | biostudies-literature
Project description: Not available
| S-DIXA-D-1031 | biostudies-other