A revised strategy for monitoring BKV-specific cellular immunity in kidney transplant patients

Weist, Benjamin; Wehler, Patrizia; Ahmad, Linda El; Schmueck-Henneresse, Michael; Millward, Jason M.; Nienen, Mikalai; Neumann, Avidan U.; Reinke, Petra; Babel, Nina

doi:10.1038/ki.2015.215

Cited by 25 publications

(26 citation statements)

References 49 publications

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“…Studies of gene expression during BK viremia and BKN have shown upregulation of cytotoxic T cell as well as NK cell-associated transcripts (20). In contrast to the predominantly CD8+ T cell response observed in our study, other investigators have found the polyfunctional CD4+ T cell response to be upregulated during viral replication (21,22), which may be related to measurement of T cell function after resolution of viremia, as CD4+ has been shown to be associated with maintenance of viral control (13). Other studies may have lacked the power to observe the polyfunctional CD8+ response as patient samples were grouped solely by phase of viremia and not by controller versus noncontroller patient status (22).…”

Section: Discussioncontrasting

confidence: 99%

Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation

Schaenman¹,

Korin

Sidwell

et al. 2017

Transplantation

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Background BK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control. Methods Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T cell activation, exhaustion, and maturation. Results BK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a. Conclusions Noninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia. 5

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Section: Discussioncontrasting

confidence: 99%

Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation

Schaenman¹,

Korin

Sidwell

et al. 2017

Transplantation

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“…These studies also suggest that CD4 ϩ T cells can control BKV reactivation even in the absence of CD8 ϩ T cell immunity (92). More recently, the same group reported that the frequency of CD4 ϩ T helper cells significantly increased before and after the clearance phase, while cytolytic CD4 ϩ cells increased during the clearance phase (93). They also reported that immunosuppressant (IS) drugs used to prevent graft rejection in KT patients can cause a reduction in the expression of cytokines, such as IFN-␥ and TNF, by BKV-specific T cells.…”

Section: Adaptive Immune Responsementioning

confidence: 88%

BK Polyomavirus: Clinical Aspects, Immune Regulation, and Emerging Therapies

et al. 2017

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BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal clinical implications. However, reactivation of BKV in immunocompromised individuals following renal or hematopoietic stem cell transplantation may cause serious complications, including BKV-associated nephropathy (BKVAN), ureteric stenosis, or hemorrhagic cystitis. Implementation of more potent immunosuppression and increased posttransplant surveillance has resulted in a higher incidence of BKVAN. Antiviral immunity plays a crucial role in controlling BKV replication, and our increasing knowledge about host-virus interactions has led to the development of improved diagnostic tools and clinical management strategies. Currently, there are no effective antiviral agents for BKV infection, and the mainstay of managing reactivation is reduction of immunosuppression. Development of immune-based therapies to combat BKV may provide new and exciting opportunities for the successful treatment of BKV-associated complications.

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“…The presence of BKV specific cells was also investigated in the renal tissue of individuals with histological confirmation of BKVN. In addition to the increased population of virus-specific T-cells, an increased presence of T cell clones, associated with alloreactive immune response, involved in tissue damage was found 17 .…”

Section: T Cell Responsementioning

confidence: 99%

“…16 ). Even in the absence of CD8, BKV reactivation can be controlled by CD4 T cells 17 . The occurrence of CD4 helpers increases significantly before and after the clearance phase, while cytolytic CD4 cells grow during this phase.…”

Section: T Cell Responsementioning

confidence: 99%

BK virus-induced renal allograft nephropathy

Krejčí¹,

Tichý²,

Bednaříková³

et al. 2018

BIOMED PAP

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BK virus nephropathy (BKVN) is a serious opportunistic infection threatening renal function especially during the first year after transplantation. Its incidence is now on the rise and is closely related to the level of the recipient's immune system inhibition. This is more intensive with current trends in transplantation medicine, where more potent immunosuppressive protocols are used and more aggressive antirejection therapy is applied. In the absence of BK virus (BKV) specific therapy and limited treatment options for advanced BKVN, active screening of BKV replication and subsequent preemptive adjustment of immunosuppression are essential measures to prevent BKVN. However, it remains unclear how to modify immunosuppressive protocols as well as how to address initial stages of BKV replication. This comprehensive review summarizes the currently applied and not completely uniform procedures for the detection, prophylaxis and therapy of BKV replication and BKVN. The pitfalls brought by reduced immunosuppression, as a typical response to a significant viral replication or a developed BKVN, are also mentioned, particularly in the form of graft rejection. The paper also outlines the authors' experiences, and lists currently ongoing studies on the subject. The perspectives of new, especially immune-based, procedures in the treatment of complications associated with BKV infections are highlighted. Different views on the management of patients indicated for kidney re-transplantation whose previous graft failed because of BKVN are also discussed.

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A revised strategy for monitoring BKV-specific cellular immunity in kidney transplant patients

Cited by 25 publications

References 49 publications

Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation

Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation

BK Polyomavirus: Clinical Aspects, Immune Regulation, and Emerging Therapies

BK virus-induced renal allograft nephropathy

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