Skip to main content
Top
Published in: BMC Infectious Diseases 1/2019

Open Access 01-12-2019 | Kidney Transplantation | Research article

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

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

Published in: BMC Infectious Diseases | Issue 1/2019

Login to get access

Abstract

Background

Adjustment of immunosuppression is the main therapy for BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) after kidney transplantation (KT). Studies of BKPyV-specific T cell immune response are scarce. Here, we investigated BKPyV-specific T cell immunity in KT recipients diagnosed with BKPyVAN.

Methods

All adult KT recipients with BKPyVAN diagnosed at our institution from January 2017 to April 2018 were included. Laboratory-developed intracellular cytokine assays measuring the percentage of IFN-γ-producing CD4+ and CD8+ T cells, after stimulation with large-T antigen (LT) and viral capsid protein 1 (VP1), were performed both at the time of diagnosis and after adjustment of immunosuppression.

Results

We included 12 KT recipients diagnosed with BKPyVAN (7 proven, 4 presumptive, and 1 possible). Those with presumptive BKPyVAN had a median plasma BKPyV DNA load of 5.9 log10 copies/ml (interquartile range [IQR]: 4.9–6.1). Adjusted dosing of mycophenolic acid and tacrolimus with (86%) or without (14%) adjunctive therapies were implemented after diagnosis. There was a significantly higher median percentage of IFN-γ-producing CD4+ T cells to LT at a median of 3 (IQR: 1–4) months after adjustment of immunosuppression compared with at the time of diagnosis (0.004 vs. 0.015; p = 0.047). However, the difference between the median percentage of IFN-γ-producing CD4+ T cells to VP1 and CD8+ T cells to LT and VP1 did not reach statistical significance. Four (33%) patients achieved plasma BKPyV DNA clearance, and the remaining eight (67%) patients had persistent BKPyV DNAemia. Although eight (67%) patients developed allograft dysfunction, none required hemodialysis.

Conclusions

We observed a marginal trend of BKPyV-specific CD4+ T cell recovery after adjustment of immunosuppression in KT recipients diagnosed with BKPyVAN. A further study would be benefited to confirm and better assess BKPyV-specific immune response after KT.
Literature
1.
go back to reference Hirsch HH, Randhawa PS. AST Infectious Diseases Community of Practice BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;12:e13528. Hirsch HH, Randhawa PS. AST Infectious Diseases Community of Practice BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;12:e13528.
2.
go back to reference Costa C, Cavallo R. Polyomavirus-associated nephropathy. World J Transplant. 2012;2:84–94.CrossRef Costa C, Cavallo R. Polyomavirus-associated nephropathy. World J Transplant. 2012;2:84–94.CrossRef
3.
go back to reference Yooprasert P, Rotjanapan P. BK virus-associated nephropathy: current situation in a resource-limited country. Transplant Proc. 2018;50:130–6.CrossRef Yooprasert P, Rotjanapan P. BK virus-associated nephropathy: current situation in a resource-limited country. Transplant Proc. 2018;50:130–6.CrossRef
4.
go back to reference Sawinski D, Goral S. BK virus infection: an update on diagnosis and treatment. Nephrol Dial Transplant. 2015;30:209–17.CrossRef Sawinski D, Goral S. BK virus infection: an update on diagnosis and treatment. Nephrol Dial Transplant. 2015;30:209–17.CrossRef
5.
go back to reference Rekvig OP, Bendiksen S, Moens U. Immunity and autoimmunity induced by polyomaviruses: clinical, experimental and theoretical aspects. Adv Exp Med Biol. 2006;577:117–47.CrossRef Rekvig OP, Bendiksen S, Moens U. Immunity and autoimmunity induced by polyomaviruses: clinical, experimental and theoretical aspects. Adv Exp Med Biol. 2006;577:117–47.CrossRef
6.
go back to reference Ambalathingal GR, Francis RS, Smyth MJ, Smith C, Khanna R. BK polyomavirus: clinical aspects, immune regulation, and emerging therapies. Clin Microbiol Rev. 2017;30:503–28.CrossRef Ambalathingal GR, Francis RS, Smyth MJ, Smith C, Khanna R. BK polyomavirus: clinical aspects, immune regulation, and emerging therapies. Clin Microbiol Rev. 2017;30:503–28.CrossRef
7.
go back to reference Leboeuf C, Wilk S, Achermann R, Binet I, Golshayan D, Hadaya K, et al. BK polyomavirus-specific 9mer CD8 T cell responses correlate with clearance of BK viremia in kidney transplant recipients: first report from the Swiss transplant cohort study. Am J Transplant. 2017;17:2591–600.CrossRef Leboeuf C, Wilk S, Achermann R, Binet I, Golshayan D, Hadaya K, et al. BK polyomavirus-specific 9mer CD8 T cell responses correlate with clearance of BK viremia in kidney transplant recipients: first report from the Swiss transplant cohort study. Am J Transplant. 2017;17:2591–600.CrossRef
8.
go back to reference Schachtner T, Stein M, Babel N, Reinke P. The loss of BKV-specific immunity from pretransplantation to posttransplantation identifies kidney transplant recipients at increased risk of BKV replication. Am J Transplant. 2015;15:2159–69.CrossRef Schachtner T, Stein M, Babel N, Reinke P. The loss of BKV-specific immunity from pretransplantation to posttransplantation identifies kidney transplant recipients at increased risk of BKV replication. Am J Transplant. 2015;15:2159–69.CrossRef
9.
go back to reference DeWolfe D, Gandhi J, Mackenzie MR, Broge TA Jr, Bord E, Babwah A, et al. Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients. PLoS One. 2017;12:e0177339.CrossRef DeWolfe D, Gandhi J, Mackenzie MR, Broge TA Jr, Bord E, Babwah A, et al. Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients. PLoS One. 2017;12:e0177339.CrossRef
10.
go back to reference Sester M, Leboeuf C, Schmidt T, Hirsch HH. The “ABC” of virus-specific T cell immunity in solid organ transplantation. Am J Transplant. 2016;16:1697–706.CrossRef Sester M, Leboeuf C, Schmidt T, Hirsch HH. The “ABC” of virus-specific T cell immunity in solid organ transplantation. Am J Transplant. 2016;16:1697–706.CrossRef
11.
go back to reference Kim T, Lee HJ, Kim SM, Jung JH, Shin S, Kim YH, et al. Diagnostic usefulness of the cytomegalovirus (CMV)-specific T cell-based assay for predicting CMV infection after kidney transplant. Korean J Intern Med. 2018. Kim T, Lee HJ, Kim SM, Jung JH, Shin S, Kim YH, et al. Diagnostic usefulness of the cytomegalovirus (CMV)-specific T cell-based assay for predicting CMV infection after kidney transplant. Korean J Intern Med. 2018.
12.
go back to reference Kumar D, Mian M, Singer L, Humar A. An interventional study using cell-mediated immunity to personalize therapy for cytomegalovirus infection after transplantation. Am J Transplant. 2017;17:2468–73.CrossRef Kumar D, Mian M, Singer L, Humar A. An interventional study using cell-mediated immunity to personalize therapy for cytomegalovirus infection after transplantation. Am J Transplant. 2017;17:2468–73.CrossRef
13.
go back to reference Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, et al. The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2018;102:900–31.CrossRef Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, et al. The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2018;102:900–31.CrossRef
14.
15.
go back to reference Ramaswami B, Popescu I, Macedo C, Luo C, Shapiro R, Metes D, et al. The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response. Clin Vaccine Immunol. 2011;18:815–24.CrossRef Ramaswami B, Popescu I, Macedo C, Luo C, Shapiro R, Metes D, et al. The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response. Clin Vaccine Immunol. 2011;18:815–24.CrossRef
16.
go back to reference Weist BJ, Schmueck M, Fuehrer H, Sattler A, Reinke P, Babel N. The role of CD4(+) T cells in BKV-specific T cell immunity. Med Microbiol Immunol. 2014;203:395–408.CrossRef Weist BJ, Schmueck M, Fuehrer H, Sattler A, Reinke P, Babel N. The role of CD4(+) T cells in BKV-specific T cell immunity. Med Microbiol Immunol. 2014;203:395–408.CrossRef
17.
go back to reference Binggeli S, Egli A, Schaub S, Binet I, Mayr M, Steiger J, et al. Polyomavirus BK-specific cellular immune response to VP1 and large T-antigen in kidney transplant recipients. Am J Transplant. 2007;7:1131–9.CrossRef Binggeli S, Egli A, Schaub S, Binet I, Mayr M, Steiger J, et al. Polyomavirus BK-specific cellular immune response to VP1 and large T-antigen in kidney transplant recipients. Am J Transplant. 2007;7:1131–9.CrossRef
18.
go back to reference Schmidt T, Adam C, Hirsch HH, et al. BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication. Am J Transplant. 2014;14:1334–45.CrossRef Schmidt T, Adam C, Hirsch HH, et al. BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication. Am J Transplant. 2014;14:1334–45.CrossRef
19.
go back to reference Egli A, Kohli S, Dickenmann M, Hirsch HH. Inhibition of polyomavirus BK-specific T-cell responses by immunosuppressive drugs. Transplantation. 2009;88:1161–8.CrossRef Egli A, Kohli S, Dickenmann M, Hirsch HH. Inhibition of polyomavirus BK-specific T-cell responses by immunosuppressive drugs. Transplantation. 2009;88:1161–8.CrossRef
20.
go back to reference Skulratanasak P, Mahamongkhonsawata J, Chayakulkeereeb M, Larpparisutha N, Premasathiana N, Vongwiwatana A. BK Virus Infection in Thai Kidney Transplant Recipients: A Single-Center Experience. Transplant Proc. 2018;50(4):1077–9.CrossRef Skulratanasak P, Mahamongkhonsawata J, Chayakulkeereeb M, Larpparisutha N, Premasathiana N, Vongwiwatana A. BK Virus Infection in Thai Kidney Transplant Recipients: A Single-Center Experience. Transplant Proc. 2018;50(4):1077–9.CrossRef
21.
go back to reference Funk GA, Steiger J, Hirsch HH. Rapid dynamics of Polyomavirus type BK in renal transplant recipients. J Infect Dis. 2006 Jan 1;193(1):80–7.CrossRef Funk GA, Steiger J, Hirsch HH. Rapid dynamics of Polyomavirus type BK in renal transplant recipients. J Infect Dis. 2006 Jan 1;193(1):80–7.CrossRef
Metadata
Title
BK Polyomavirus-specific T cell immune responses in kidney transplant recipients diagnosed with BK Polyomavirus-associated nephropathy
Authors
Jackrapong Bruminhent
Supranart Srisala
Chompunut Klinmalai
Subencha Pinsai
Siriorn P. Watcharananan
Surasak Kantachuvesiri
Suradej Hongeng
Nopporn Apiwattanakul
Publication date
01-12-2019

Other articles of this Issue 1/2019

BMC Infectious Diseases 1/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.