<i>MICA</i>Mutant A5.1 Influences BK Polyomavirus Reactivation and Associated Nephropathy After Kidney Transplantation

Tonnerre, Pierre; Gérard, Nathalie; Gavlovsky, Pierre-Jean; Mazalrey, Simon; Hourmant, Maryvonne; Cheneau, M.L.; Cesbron‐Gautier, Anne; Renaudin, Karine; Bressollette-Bodin, Céline; Charreau, Béatrice

doi:10.1093/infdis/jiw168

Cited by 8 publications

(9 citation statements)

References 43 publications

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“…Two decades after the report of Pappo et al and despite general outcome improvements, the care of patients with PyVAN remains a daunting task, mostly due to the complexity of immunological responses and poorly understood factors influencing the susceptibility to the infection .…”

Section: Discussionmentioning

confidence: 99%

Histological Evolution of BK Virus–Associated Nephropathy: Importance of Integrating Clinical and Pathological Findings

Drachenberg

Chaudhry

Ugarte

et al. 2017

American Journal of Transplantation

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Long-term clinicopathological studies of BK-associated nephropathy (PyVAN) are not available. We studied 206 biopsies (71 patients), followed 3.09 ± 1.46 years after immunosuppression reduction. The biopsy features (% immunostain for PyV large T ag + staining and inflammation ± acute rejection) were correlated with viral load dynamics and serum creatinine to define the clinicopathological status (PyVCPS). Incidence of acute rejection was 28% in the second biopsy and 50% subsequently (25% mixed T cell-mediated allograft rejection (TCMR) + antibody-mediated allograft rejection (AMR); rejection overall affected 38% of patients (>50% AMR). Graft loss was 15.4% (0.8-5.3 years after PyVAN); 76% had complete viral clearance (mean 28 weeks). The only predictors of graft loss were acute rejection (TCMR p = 0.008, any type p = 0.07), and increased "t" and "ci" in the second biopsy (p = 0.006 and 0.048). Higher peak viremia correlated with poorer viral clearance (p = 0.002). Presumptive and proven PyVAN had similar presentation, evolution, and outcome. Late PyVAN (>2 years, 9.8%) justifies BK viremia evaluation at any point with graft dysfunction and/or biopsy evaluation. This study describes the histological evolution of PyVAN and corresponding clinicopathological correlations. Although the pathological features overall reflect the viral and immunological interactions, the PyVAN course remains difficult to predict based on any single feature. Appropriate clinical management requires repeat biopsies and determination of the PyVCPS at relevant time points, for corresponding personalized immunosuppression adjustment.

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Section: Discussionmentioning

confidence: 99%

Histological Evolution of BK Virus–Associated Nephropathy: Importance of Integrating Clinical and Pathological Findings

Drachenberg

Chaudhry

Ugarte

et al. 2017

American Journal of Transplantation

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“…About BK virus, Tonnerre et al . found a lower incidence of BK virus reactivation in recipient transplanted with renal graft carrying MICA A5.1 mutant (a ligand for the activating NK receptor NKG2D) . These data suggest that intragraft MICA expression may a significant incidence on BK virus reactivation after transplantation and may indicate a protective role for MICA A5.1.…”

Section: Discussionmentioning

confidence: 76%

“…In a group of 90 CMV-negative patients having received a first renal transplantation from a CMV-positive donor, there was no significant difference between the KIR A and B haplotypes or the number of activating or inhibitory KIRs in terms of the occurrence of CMV disease [13]. About BK virus, Tonnerre et al found a lower incidence of BK virus reactivation in recipient transplanted with renal graft carrying MICA A5.1 mutant (a ligand for the activating NK receptor NKG2D) [14]. These data suggest that intragraft MICA expression may a significant incidence on BK virus reactivation after transplantation and may indicate a protective role for MICA A5.1.…”

Section: Discussionmentioning

confidence: 98%

The association between killer-cell immunoglobulin-like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

et al. 2016

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BK virus is a common opportunistic post-transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two-year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin-like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post-transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.

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“…Stress conditions following transplantation cause a general inflammatory status in recipients, which could increase MICA production. In kidney allografts, an enhanced MICA expression has been reported on epithelial and endothelial cells in response to ischemia-reperfusion injury, acute rejection, or viral infection ( 27 , 37 ). Thus, the presence of MICA in the donor organ could elicit NK and T cell activating responses via the NKG2D receptor.…”

Section: Discussionmentioning

confidence: 99%

“…A CMV transmission to allograft recipients may occur via donor organs as the virus is able to infect several types of human kidney cells and thus can reside in the graft ( 36 ). In contrast to other tissues, a notably strong MICA protein expression has been described in kidney allografts ( 37 , 38 ). Consequently, MICA/NKG2D axis polymorphisms of the donor organ or the recipient may affect immune antiviral NK and T cell responses against CMV.…”

Section: Introductionmentioning

confidence: 99%

The Donor Major Histocompatibility Complex Class I Chain-Related Molecule A Allele rs2596538 G Predicts Cytomegalovirus Viremia in Kidney Transplant Recipients

et al. 2018

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The interaction of major histocompatibility complex class I chain-related protein A (MICA) and its cognate activating receptor natural killer (NK) group 2 member D (NKG2D) receptor plays a significant role in viral immune control. In the context of kidney transplantation (KTx), cytomegalovirus (CMV) frequently causes severe complications. Hypothesizing that functional polymorphisms of the MICA/NKG2D axis might affect antiviral NK and T cell responses to CMV, we explored the association of the MICA-129 Met/Val single nucleotide polymorphism (SNP) (affecting the binding affinity of MICA with the NKG2D receptor), the MICA rs2596538 G/A SNP (influencing MICA transcription), and the NKG2D rs1049174 G/C SNP (determining the cytotoxic potential of effector cells) with the clinical outcome of CMV during the first year after KTx in a cohort of 181 kidney donor-recipients pairs. Univariate analyses identified the donor MICA rs2596538 G allele status as a protective prognostic determinant for CMV disease. In addition to the well-known prognostic factors CMV high-risk sero-status of patients and the application of lymphocyte-depleting drugs, the donor MICA rs2596538 G allele carrier status was confirmed by multivariate analyses as novel-independent factor predicting the development of CMV infection/disease during the first year after KTx. The results of our study emphasize the clinical importance of the MICA/NKG2D axis in CMV control in KTx and point out that the potential MICA transcription in the donor allograft is of clinically relevant importance for CMV immune control in this allogeneic situation. Furthermore, they provide substantial evidence that the donor MICA rs2596538 G allele carrier status is a promising genetic marker predicting CMV viremia after KTx. Thus, in the kidney transplant setting, donor MICA rs2596538 G may help to allow the future development of personal CMV approaches within a genetically predisposed patient cohort.

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MICAMutant A5.1 Influences BK Polyomavirus Reactivation and Associated Nephropathy After Kidney Transplantation

Abstract: These findings identify the MHC-related MICA as an immunogenetic factor that may functionally influence anti-BKPyV immune responses and infection outcomes.

Cited by 8 publications

References 43 publications

Histological Evolution of BK Virus–Associated Nephropathy: Importance of Integrating Clinical and Pathological Findings

Histological Evolution of BK Virus–Associated Nephropathy: Importance of Integrating Clinical and Pathological Findings

The association between killer-cell immunoglobulin-like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

The Donor Major Histocompatibility Complex Class I Chain-Related Molecule A Allele rs2596538 G Predicts Cytomegalovirus Viremia in Kidney Transplant Recipients

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