BK Polyomavirus-specific T cell immune responses in kidney transplant recipients diagnosed with BK Polyomavirus-associated nephropathy

Bruminhent, Jackrapong; Srisala, Supranart; Klinmalai, Chompunut; Pinsai, Subencha; Watcharananan, Siriorn P.; Kantachuvesiri, Surasak; Hongeng, Suradej; Apiwattanakul, Nopporn

doi:10.1186/s12879-019-4615-x

Cited by 12 publications

(14 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lack of either global innate or CMV-specific adaptive immunity has been described as a poor prognostic factor for CMV reactivation after SOT [ 14 ]. The restoration of viral-specific cell-mediated immunity is associated with viral clearance, and, conversely, the failure of this immunity is associated with uncontrolled infection by viruses such as adenovirus, BK polyomavirus, and CMV [ 8 , 15 , 16 ]. However, the measurement of viral-specific cell-mediated immunity is not universally available, and its accessibility is low compared with the measurement of anti-CMV IgG titer.…”

Section: Discussionmentioning

confidence: 99%

Predictors of CMV Infection in CMV-Seropositive Kidney Transplant Recipients: Impact of Pretransplant CMV-Specific Humoral Immunity

Kirisri

Vongsakulyanon

Kantachuvesiri

et al. 2021

Open Forum Infectious Diseases

Self Cite

View full text Add to dashboard Cite

Introduction Although cytomegalovirus (CMV)-seropositive solid organ transplant recipients have a relatively lower risk of CMV infection than CMV-seronegative recipients who receive allograft from CMV-seropositive donors, some patients remain at risk of CMV infection after transplant. We investigated the pre-transplant CMV-specific humoral immunity (CHI) and other CMV infection predictors in CMV-seropositive kidney transplant (KT) recipients. Methods This retrospective study was conducted on adult CMV-seropositive KT recipients during 2017 and 2018. The cumulative incidence of CMV infection was estimated with Kaplan–Meier methodology. CHI, measured with an enzyme-linked fluorescent immunoassay and other predictors for CMV infection, was analyzed using Cox proportional hazards models. Results Of the 340 CMV-seropositive KT recipients (37% female; age [mean ± SD]: 43±11 years), 69% received deceased-donor allograft and 64% received induction therapy. During a mean follow-up of 14 months, the cumulative incidence of CMV infection was 14.8%. In multivariate analysis, low pre-transplant CHI (defined as anti-CMV IgG titer <20 AU/ml) was significantly associated with CMV infection (HR, 2.98; 95% CI, 1.31–6.77, [p=0.009]). Other significant predictors of CMV infection included older donor age (HR, 1.03; 95% CI, 1.01–1.06, [p=0.005]), anti-thymocyte induction therapy (HR, 2.90; 95% CI 1.09–7.74, [p=0.033]), and prolonged cold ischemic time (HR, 1.06; 95% CI, 1.02–1.10, [p=0.002]). Conclusion A low pre-transplant CHI is independently associated with post-transplant CMV infection in CMV-seropositive KT recipients. A quantitative anti-CMV IgG assay could potentially stratify CMV-seropositive patients at risk of CMV infection after KT.

show abstract

Section: Discussionmentioning

confidence: 99%

Predictors of CMV Infection in CMV-Seropositive Kidney Transplant Recipients: Impact of Pretransplant CMV-Specific Humoral Immunity

Kirisri

Vongsakulyanon

Kantachuvesiri

et al. 2021

Open Forum Infectious Diseases

Self Cite

View full text Add to dashboard Cite

show abstract

“…There is currently no approved antiviral therapy with clinical efficacy against BKPyV, so presumptive or biopsy-confirmed PyVAN is managed by modulation of immunosuppressive therapy, which allows host immune responses to clear the virus [ 7 ]. The virological response rate to this intervention appears to vary between centres, with recent publications reporting clearance of viremia in response to modulation of immunosuppression in proportions varying from 30% [ 8 , 9 ] up to more than 75% [ 10 ] of PyVAN patients. In the single-centre study with the longest follow-up and the largest cohort, clearance of viremia was attained by 44 (92%) of 48 patients with presumptive PyVAN following a standard three-stage protocol for reduction of immunosuppressive therapy [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Persistent BK Polyomavirus Viruria Is Associated with Accumulation of VP1 Mutations and Neutralization Escape

McIlroy

Hönemann

Nguyen

et al. 2020

Viruses

View full text Add to dashboard Cite

To investigate the relationship between neutralization escape and persistent high-level BK polyomavirus replication after kidney transplant (KTx), VP1 sequences were determined by Sanger and next-generation sequencing in longitudinal samples from KTx recipients with persistent high-level viruria (non-controllers) compared to patients who suppressed viruria (controllers). The infectivity and neutralization resistance of representative VP1 mutants were investigated using pseudotype viruses. In all patients, the virus population was initially dominated by wild-type VP1 sequences, then non-synonymous VP1 mutations accumulated over time in non-controllers. BC-loop mutations resulted in reduced infectivity in 293TT cells and conferred neutralization escape from cognate serum in five out of six non-controller patients studied. When taken as a group, non-controller sera were not more susceptible to neutralization escape than controller sera, so serological profiling cannot predict subsequent control of virus replication. However, at an individual level, in three non-controller patients the VP1 variants that emerged exploited specific “holes” in the patient’s humoral response. Persistent high-level BK polyomavirus replication in KTx recipients is therefore associated with the accumulation of VP1 mutations that can confer resistance to neutralization, implying that future BKPyV therapies involving IVIG or monoclonal antibodies may be more effective when used as preventive or pre-emptive, rather than curative, strategies.

show abstract

“…13 The decline in viral-speci c T-cell immunity has been shown to increase the risk of various infections, such as adenovirus, BKPyV, and CMV infections, in transplant recipients. [13][14][15][16] While most studies have investigated the role of CMV-speci c T-cell immunity and applied their ndings in clinical practice via a commercial test, such as the QuantiFERON-CMV assay, there are limited studies on BKPyV-speci c immunity 17,18 , which has left the mechanism of BKPyV persistence and reactivation unclear. 8…”

Section: Discussionmentioning

confidence: 99%

Clinical and Immunological Characteristics for BK Polyomavirus- associated Nephropathy after Kidney Transplantation

Siripoon

Apiwattanakul

Mongkolrattanakul

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) could cause allograft dysfunction among kidney transplant (KT) recipients. Intact BKPyV-specific immunity is correlated with viral containment, therefore clinical and immunological characteristics related to BKVAN after KT needs to be explored. Methods We prospectively investigated an association between clinical baseline characteristics, BK polyomavirus (BKPyV)-specific immunity, and BKPyV-associated nephropathy (BKPyVAN) in KT recipients. BKPyV-specific immunity, measured with intracellular cytokine assays, is reported as the percentage of IFN-γ-producing CD4+ T, CD8+ T, natural killer (NK), and NKT cells after large-T antigen and viral capsid protein 1 (VP1) stimulation. Results Among 100 KT patients, BKPyVAN occurred in 18% within one-year post-KT. There were 70 patients (70%) who received an induction immunosuppressive therapy. Diabetic nephropathy was significantly associated with BKPyVAN. Among 40 patients who were eligible for the immunological study. In a multivariate analysis, pre-KT %VP1-specific NK cells were independently associated with BKPyVAN (HR, 1.209; 95%CI, 1.055–1.386; P = 0.006). In those with BKPyVAN, the mean %NK (coefficient, 1.202; 95%CI, 0.033–2.371; P = 0.04), %VP1-specific NK (coefficient, 2.602; 95%CI, 1.083–4.121; P = 0.001), and %NKT (coefficient, 0.199; 95%CI, 0.051–0.348; P = 0.008) cells at 1-month post-KT were significantly higher than those pre-KT. Thus, increasing NK, VP1-specific NK, and NKT cell proportions were observed among KT recipients who developed BKPyVAN within the first year. Conclusion KT recipients with underlying diabetes and the presence of BKPyV-specific NK- and NKT-cell immunity could be at risk of BKPyVAN after KT. BKPyV-specific innate immune monitoring could potentially stratify those at risk of BKPyVAN among KT recipients. (Thai Clinical Trials Registry, TCTR20190404004)

show abstract

BK Polyomavirus-specific T cell immune responses in kidney transplant recipients diagnosed with BK Polyomavirus-associated nephropathy

Cited by 12 publications

References 22 publications

Predictors of CMV Infection in CMV-Seropositive Kidney Transplant Recipients: Impact of Pretransplant CMV-Specific Humoral Immunity

Predictors of CMV Infection in CMV-Seropositive Kidney Transplant Recipients: Impact of Pretransplant CMV-Specific Humoral Immunity

Persistent BK Polyomavirus Viruria Is Associated with Accumulation of VP1 Mutations and Neutralization Escape

Clinical and Immunological Characteristics for BK Polyomavirus- associated Nephropathy after Kidney Transplantation

Contact Info

Product

Resources

About