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BK Polyomavirus Nephropathy in Kidney Transplantation: Balancing Rejection and Infection.

ABSTRACT: BK polyomavirus nephropathy (BKVN) and allograft rejection are two closely-associated diseases on opposite ends of the immune scale in kidney transplant recipients. The principle of balancing the immune system remains the mainstay of therapeutic strategy. While patient outcomes can be improved through screening, risk factors identification, and rapid reduction of immunosuppressants, a lack of standard curative therapy is the primary concern during clinical practice. Additionally, difficulty in pathological differential diagnosis and clinicopathology's dissociation pose problems for a definite diagnosis. This article discusses the delicate evaluation needed to optimize immunosuppression and reviews recent advances in molecular diagnosis and immunological therapy for BKVN patients. New biomarkers for BKVN diagnosis are under development. For example, measurement of virus-specific T cell level may play a role in steering immunosuppressants. The development of cellular therapy may provide prevention, even a cure, for BKVN, a complex post-transplant complication.

SUBMITTER: Shen CL

PROVIDER: S-EPMC7998398 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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BK Polyomavirus Nephropathy in Kidney Transplantation: Balancing Rejection and Infection.

Shen Chia-Lin CL Wu Bo-Sheng BS Lien Tse-Jen TJ Yang An-Hang AH Yang Chih-Yu CY

Viruses 20210316 3

BK polyomavirus nephropathy (BKVN) and allograft rejection are two closely-associated diseases on opposite ends of the immune scale in kidney transplant recipients. The principle of balancing the immune system remains the mainstay of therapeutic strategy. While patient outcomes can be improved through screening, risk factors identification, and rapid reduction of immunosuppressants, a lack of standard curative therapy is the primary concern during clinical practice. Additionally, difficulty in p ...[more]

PMID: 33809472

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Project description:Abstract Introduction BK polyomavirus (BKPyV)‐associated nephropathy (BKPyVAN) can cause a significant risk of allograft impairment after kidney transplantation (KT). Intact BKPyV‐specific immunity is associated with viral containment. This study investigated BKPyV‐specific immunological factors among KT recipients. Methods This prospective study in a single transplant center from January 2019 to August 2019 assessed associations between clinical and immunological characteristics, with a focus on BKPyV‐cell‐specific immunity and BKPyVAN, among KT recipients aged ≥15 years. The numbers of interferon‐gamma (IFN‐γ)‐producing CD4+ T, CD8+ T, natural killer (NK), and natural killer T (NKT) cells were measured after stimulation with large T antigen and viral capsid protein 1 (VP1). Results In total, 100 KT recipients were included (mean age ± SD, 42 ± 11 years); 35% of the recipients were female patients, and 70% had received induction immunosuppressive therapy. The 1‐year cumulative incidence of high‐level BKPyV DNAuria (possible BKPyVAN) and (presumptive BKPyVAN) was 18%. Among 40 patients with immunological factor data, pre‐KT %NK cells (hazard ratio [HR], 1.258; 95% confidence interval [CI], 1.077–1.469; p = .004) and %VP1‐specific NK cells (HR, 1.209; 95% CI, 1.055–1.386; p = .006) were factors independently associated with possible and presumptive BKPyVAN. KT recipients with possible and presumptive BKPyVAN were more likely to exhibit significant mean coefficients of %NK, %VP1‐specific NK, and %NKT cells at 1 month after KT than before KT (all p < .05). Conclusion Individuals with nonspecific and VP1‐specific NK cells before KT and increasing numbers of these cells after KT may be at risk for high‐level BKPyV DNAuria and presumptive BKPyVAN. Further studies are needed to determine the utility of BKPyV‐specific innate immune surveillance in predicting the occurrence of BKPyVAN. Initial levels and post‐KT increases in NK, NKT, and VP1‐specific NK cells were greater in KT recipients who exhibited BKPyV DNAuria within 1 year after KT. BKPyV‐specific NK‐ and NKT‐cell immune surveillance could be used to identify patients at risk for post‐transplant viral reactivation.

Dataset Information

BK Polyomavirus Nephropathy in Kidney Transplantation: Balancing Rejection and Infection.

Publications

BK Polyomavirus Nephropathy in Kidney Transplantation: Balancing Rejection and Infection.

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