Dataset Information

Immunologic Clearance of a BK Virus-associated Metastatic Renal Allograft Carcinoma.

ABSTRACT:

Background

Metastatic carcinoma of a renal allograft is a rare but life threatening event with a difficult clinical management. Recent reports suggested a potential role of BK polyomavirus (BKPyV) in the development of urologic tract malignancies in kidney transplant recipients.

Methods

We investigated a kidney-pancreas female recipient with an history of BKPyV nephritis who developed a rapidly progressive and widely metastatic donor-derived renal carcinoma 9 years after transplantation.

Results

Histology and fluorescence in situ hybridization analysis revealed a donor-derived (XY tumor cells) collecting (Bellini) duct carcinoma. The presence of BKPyV oncogenic large tumor antigen was identified in large amount within the kidney tumor and the bowel metastases. Whole genome sequencing of the tumor confirmed multiple genome BKPyV integrations. The transplanted kidney was removed, immunosuppression was withdrawn, and recombinant interleukin-2 (IL-2) was administered for 3 months, inducing a complete tumor clearance, with no evidence of disease at 6-year follow-up. The immunological profiling during IL-2 therapy revealed the presence of donor-specific T cells and expanded cytokine-producing bright natural killer cells but no donor-specific antibodies. Finally, we found persistently elevated anti-BK virus IgG titers and a specific anti-BKPyV T cell response.

Conclusions

This investigation showed evidence for the potential oncogenic role of BKPyV in collecting duct carcinoma in renal allografts and demonstrated that immunosuppression withdrawal and IL-2 therapy can lead to an efficient antitumor cellular mediated rejection possibly via 3 distinct mechanisms including (1) host-versus-graft, (2) host-versus-tumor, and (3) anti-BKPyV responses.

SUBMITTER: Meier RPH

PROVIDER: S-EPMC7837753 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Immunologic Clearance of a BK Virus-associated Metastatic Renal Allograft Carcinoma.

Meier Raphael P H RPH Muller Yannick D YD Dietrich Pierre-Yves PY Tille Jean-Christophe JC Nikolaev Sergey S Sartori Ambra A Labidi-Galy Intidhar I Ernandez Thomas T Kaur Amandeep A Hirsch Hans H HH McKee Thomas A TA Toso Christian C Villard Jean J Berney Thierry T

Transplantation 20210201 2

<h4>Background</h4>Metastatic carcinoma of a renal allograft is a rare but life threatening event with a difficult clinical management. Recent reports suggested a potential role of BK polyomavirus (BKPyV) in the development of urologic tract malignancies in kidney transplant recipients.<h4>Methods</h4>We investigated a kidney-pancreas female recipient with an history of BKPyV nephritis who developed a rapidly progressive and widely metastatic donor-derived renal carcinoma 9 years after transplan ...[more]

PMID: 32091486

Similar Datasets

Project description:BackgroundReactivation of BK polyoma virus causes a destructive virus allograft nephropathy (BKVAN) with graft loss in 46%. Treatment options are limited to reduced immunosuppression and largely ineffective antiviral agents. Some studies suggest benefit from intravenous immunoglobulin (IVIG).MethodsWe evaluated effectiveness of adjuvant IVIG to eliminate virus from blood and tissue, in a retrospective, single-center cohort study, against standard-of-care controls. Both groups underwent reduced immunosuppression; conversion of tacrolimus to cyclosporine; and mycophenolate to leflunomide, oral ciprofloxacin, and intravenous cidofovir.ResultsBiopsy-proven BKVAN occurred in 50 kidneys at 7 (median interquartile range, 3-12) months after transplantation, predominantly as histological stage B (92%), diagnosed following by dysfunction in 46%, screening viremia in 20%, and protocol biopsy in 34%. After treatment, mean viral loads fell from 1581 ± 4220 × 103 copies at diagnosis to 1434 ± 70 639 midtreatment, and 0.138 ± 0.331 after 3 months (P < 0.001). IVIG at 1.01 ± 0.18 g/kg was given to 22 (44%) patients. The IVIG group more effectively cleared viremia (hazard ratio, 3.68; 95% confidence interval, 1.56-8.68; P = 0.003) and BK immunohistochemistry from repeated tissue sampling (hazard ratio, 2.24; 95% confidence interval, 1.09-4.58; P = 0.028), and resulted in faster (11.3 ± 10.4 months vs 29.1 ± 31.8 months, P = 0.015) and more complete resolution of viremia (33.3% vs 77.3%, P = 0.044). Numerically, fewer graft losses occurred with IVIG (27.3% vs 53.6% for control, P = 0.06), although graft and patient survivals were not statistically different. Acute renal dysfunction requiring pulse corticosteroid was common (59.1% vs 78.6%, P = 0.09), respectively, after immunosuppression reduction.ConclusionsCombination treatment incorporating adjuvant IVIG was more effective eliminating virus from BKVAN, compared with conventional therapy. Validation by multicenter randomized trial is needed.

Project description:Background and objectivesThe published tissue adequacy requirement of kidney medulla for BK virus allograft nephropathy diagnosis lacks systematic verification and competes against potential increased procedural risks from deeper sampling.Design, setting, participants, & measurementsWe evaluated whether the presence of kidney medulla improved the diagnostic rate of BK nephropathy in 2244 consecutive biopsy samples from 856 kidney transplants with detailed histologic and virologic results.ResultsMedulla was present in 821 samples (37%) and correlated with maximal core length (r=0.35; P<0.001). BK virus allograft nephropathy occurred in 74 (3% overall) but increased to 5% (42 of 821) with medulla compared with 2% (32 of 1423) for cortical samples (P<0.001). Biopsy medulla was associated with infection after comprehensive multivariable adjustment of confounders, including core length, glomerular number, and number of cores (adjusted odds ratio, 1.81; 95% confidence interval, 1.02 to 3.21; P=0.04). In viremic cases (n=275), medulla was associated with BK virus nephropathy diagnosis (39% versus 19% for cortex; P<0.001) and tissue polyomavirus load (Banff polyomavirus score 0.64±0.96 versus 0.33±1.00; P=0.006). Biopsy medulla was associated with BK virus allograft nephropathy using generalized estimating equation (odds ratio, 2.04; 95% confidence interval, 1.05 to 3.96; n=275) and propensity matched score comparison (odds ratio, 2.24; 95% confidence interval, 1.11 to 4.54; P=0.03 for 156 balanced pairs). Morphometric evaluation of Simian virus 40 large T immunohistochemistry found maximal infected tubules within the inner cortex and medullary regions (P<0.001 versus outer cortex).ConclusionsActive BK virus replication concentrated around the corticomedullary junction can explain the higher detection rates for BK virus allograft nephropathy with deep sampling. The current adequacy requirement specifying targeting medulla can be justified to minimize a missed diagnosis from undersampling.

Dataset Information

Immunologic Clearance of a BK Virus-associated Metastatic Renal Allograft Carcinoma.

Background

Methods

Results

Conclusions

Publications

Immunologic Clearance of a BK Virus-associated Metastatic Renal Allograft Carcinoma.

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