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Pediatric Nephrology (Berlin, Germany) Apr 2021After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK... (Review)
Review
After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK polyomavirus (BKPyV) or Epstein-Barr virus (EBV), and less frequent from adenovirus (ADV). However, suitable predictive markers for the individual outcome of viral infections are missing and the therapeutic management remains a challenge to the success of pediatric kidney transplantation. Virus-specific T cells are known for controlling viral replication and there is growing evidence that virus-specific T cells may serve as a prognostic marker to identify patients at risk for viral complications. This review provides an overview of the usability of virus-specific T cells for improving diagnostic and therapeutic management of viral infections with reference to the necessity of antiviral prophylaxis, timing of pre-emptive therapy, and dosing of immunosuppressive medication after pediatric kidney transplantation. Several studies demonstrated that high levels of virus-specific T cells are associated with decrease of virus load and favorable outcome, whereas lack of virus-specific T cells coincided with virus-induced complications. Accordingly, the additional monitoring of virus-specific T cells aims to personalize the management of antiviral therapy, identify overimmunosuppression, and avoid unnecessary therapeutic interventions. Prospective randomized trials in pediatric kidney recipients comparing standard antiviral and immunosuppressive regimens with T cell-guided therapeutic interventions are needed, before monitoring of virus-specific T cells is implemented in the routine care of pediatric kidney graft recipients.
Topics: Antiviral Agents; BK Virus; Child; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Kidney Transplantation; Polyomavirus Infections; Prospective Studies; T-Lymphocytes
PubMed: 32221706
DOI: 10.1007/s00467-020-04522-6 -
Blood Feb 2020Viral infections are common and are potentially life-threatening in patients with moderate to severe primary immunodeficiency disorders. Because T-cell immunity... (Review)
Review
Viral infections are common and are potentially life-threatening in patients with moderate to severe primary immunodeficiency disorders. Because T-cell immunity contributes to the control of many viral pathogens, adoptive immunotherapy with virus-specific T cells (VSTs) has been a logical and effective way of combating severe viral disease in immunocompromised patients in multiple phase 1 and 2 clinical trials. Common viral targets include cytomegalovirus, Epstein-Barr virus, and adenovirus, though recent published studies have successfully targeted additional pathogens, including HHV6, BK virus, and JC virus. Though most studies have used VSTs derived from allogenic stem cell donors, the use of banked VSTs derived from partially HLA-matched donors has shown efficacy in multicenter settings. Hence, this approach could shorten the time for patients to receive VST therapy thus improving accessibility. In this review, we discuss the usage of VSTs for patients with primary immunodeficiency disorders in clinical trials, as well as future potential targets and methods to broaden the applicability of virus-directed T-cell immunotherapy for this vulnerable patient population.
Topics: Humans; Immunocompromised Host; Immunotherapy, Adoptive; Primary Immunodeficiency Diseases; T-Lymphocytes; Virus Diseases
PubMed: 31942610
DOI: 10.1182/blood.2019000924 -
Pre-Transplantation Assessment of BK Virus Serostatus: Significance, Current Methods, and Obstacles.Viruses Oct 2019The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress... (Review)
Review
The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker for post-transplantation BKPyV replication. The fact that research laboratories have used many different assay techniques to determine BKPyV serostatus complicates these data analysis. Even studies based on the same technique differed in their standard controls choice, the antigenic structure type used for detection, and the cut-off for seropositivity. Here, we review the different BKPyV VP1 antigens types used for detection and consider the various BKPyV serostatus assay techniques' advantages and disadvantages. Lastly, we highlight the obstacles in the implementation of a consensual BKPyV serologic assay in clinics (e.g., the guidelines absence in this field).
Topics: BK Virus; DNA, Viral; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Transplantation; Retrospective Studies; Serologic Tests; Transplant Recipients; Tumor Virus Infections; Viremia
PubMed: 31615131
DOI: 10.3390/v11100945 -
International Journal of Nephrology and... 2024Glomeruli can be damaged in several conditions after kidney transplantation, with a potential impact on the graft function and survival. Primary glomerulonephritis, a... (Review)
Review
Glomeruli can be damaged in several conditions after kidney transplantation, with a potential impact on the graft function and survival. Primary glomerulonephritis, a group of glomerular immunological damage that results in variable histological patterns and clinical phenotypes, can occur in kidney transplant recipients as a recurrent or de novo condition. Specific immunologic conditions associated with kidney transplantation, such as acute rejection episodes, can act as an additional trigger after transplantation, impacting the incidence of these glomerulopathies. The post-transplant GN recurrence ranges from 3% to 15%, varying according to the GN subtype and post-transplant time, mainly occurring after 3-5 years of kidney transplantation. Advances in the knowledge of glomerulonephritis pathophysiology have provided new approaches to pre-transplant risk evaluation and post-transplant monitoring. Glomeruli can be affected by several systemic viral infections, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), cytomegalovirus (CMV), and BK virus. The diagnosis of these infections, as well as the identification of possible complications associated with them, are important to minimize the negative impacts of these conditions on kidney transplant recipients' outcomes.
PubMed: 38495741
DOI: 10.2147/IJNRD.S391779 -
Reviews in Medical Virology Jul 2019BK polyomavirus (BKV) is an important cause of graft loss in renal transplant recipients that continues to pose a significant challenge to clinicians due to its... (Review)
Review
BK polyomavirus (BKV) is an important cause of graft loss in renal transplant recipients that continues to pose a significant challenge to clinicians due to its frequently unpredictable onset, persistence, and the lack of effective antiviral agents or prevention strategies. This review covers our current understanding of epidemiology, viral transmission and disease progression, and treatment and prevention strategies that have been used to manage this disease.
Topics: BK Virus; Disease Progression; Disease Transmission, Infectious; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Polyomavirus Infections
PubMed: 30958614
DOI: 10.1002/rmv.2044 -
Kidney360 May 2021Cytomegalovirus (CMV) and BK virus (BKV) are common viral infections after kidney transplant. Their negative effects on patient and graft outcomes have been well... (Review)
Review
Cytomegalovirus (CMV) and BK virus (BKV) are common viral infections after kidney transplant. Their negative effects on patient and graft outcomes have been well described. However, despite improvement in screening and prophylaxis strategies, CMV and BKV continue to negatively affect both short- and long-term graft survival. Adequate cell-mediated immunity is essential for the control and prevention of opportunistic viral infections, such as CMV and BKV. Therefore, immune reconstitution, in particular T cell recovery, is a key factor in antiviral control after kidney transplantation. Cell-based immunotherapy offers an attractive alternative approach to traditional interventions. Adoptive T cell transfer, infusions of allogeneic virus-specific T lymphocytes is capable of restoring virus-specific T cell immunity, and are safe and effective in the treatment of viral infections after hematopoietic stem cell transplantation. In this article, we review the emerging role of virus-specific T cell therapy in the management of CMV and BKV after kidney transplantation. On the basis of the available data, virus-specific T cell therapy may be a promising addition to the antiviral treatment armamentarium after kidney transplantation. Future studies are needed to more clearly define the efficacy and risks of virus-specific T cell therapy in the kidney transplant population.
Topics: BK Virus; Cytomegalovirus; Hematopoietic Stem Cell Transplantation; Humans; Kidney Transplantation; Transplant Recipients
PubMed: 35373059
DOI: 10.34067/KID.0001572021 -
World Journal of Transplantation Dec 2023BK viral infection remains to be a challenging post-transplant infection, which can result in kidney dysfunction. The mainstay approach to BK infection is reduction of... (Review)
Review
BK viral infection remains to be a challenging post-transplant infection, which can result in kidney dysfunction. The mainstay approach to BK infection is reduction of immunosuppression. Alterations in immunosuppressive regimen with minimization of calcineurin inhibitors, use of mechanistic target of rapamycin inhibitors, and leflunomide have been attempted with variable outcomes. Over the past few years, investigators have explored potential therapeutic options for BK infection. Fluoroquinolone prophylaxis and treatment was found to have no benefit in kidney transplant recipients. The utility of cidofovir is limited by its nephrotoxicity. Intravenous immunoglobulin is becoming a popular option for treatment and prophylaxis for BK infection, as it increases the neutralizing antibody titers against the most common BK virus serotypes. Virus-specific T cell therapy is an emerging treatment option for BK viremia. In this review, we will explore management and therapeutic options for BK infection and recent evidence available in literature.
PubMed: 38174153
DOI: 10.5500/wjt.v13.i6.309 -
American Journal of Transplantation :... Sep 2019
Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Humans; Polyomavirus Infections; Viremia
PubMed: 31306544
DOI: 10.1111/ajt.15531 -
Clinical Transplantation Nov 2022BK polyomavirus-associated nephropathy (BKPyVAN) carries a risk of irreversible allograft injury. While detection of BK viremia and biopsy assessment are the current...
BACKGROUND
BK polyomavirus-associated nephropathy (BKPyVAN) carries a risk of irreversible allograft injury. While detection of BK viremia and biopsy assessment are the current diagnostic gold standard, the diagnostic value of biomarkers reflecting tissue injury (donor-derived cell-free DNA [dd-cfDNA]) or immune activation (C-X-C motif chemokine ligand [CXCL]9 and CXCL10) remains poorly defined.
METHODS
For this retrospective study, 19 cases of BKPyVAN were selected from the Vienna transplant cohort (biopsies performed between 2012 and 2019). Eight patients with T cell-mediated rejection (TCMR), 17 with antibody-mediated rejection (ABMR) and 10 patients without polyomavirus nephropathy or rejection served as controls. Fractions of dd-cfDNA were quantified using next-generation sequencing and CXCL9 and CXCL10 were detected using multiplex immunoassays.
RESULTS
BKPyVAN was associated with a slight increase in dd-cfDNA (median; interquartile range: .38% [.27%-1.2%] vs. .21% [.12%-.34%] in non-rejecting control patients; p = .005). Levels were far lower than in ABMR (1.2% [.82%-2.5%]; p = .004]), but not different from TCMR (.54% [.26%-3.56%]; p = .52). Within the BKPyVAN cohort, we found no relationship between dd-cfDNA levels and the extent of tubulo-interstitial infiltrates, BKPyVAN class and BK viremia/viruria, respectively. In some contrast to dd-cfDNA, concentrations of urinary CXCL9 and CXCL10 exceeded those detected in ABMR, but similar increases were also found in TCMR.
CONCLUSION
BKPyVAN can induce moderate increases in dd-cfDNA and concomitant high urinary excretion of chemokines, but this pattern may be indistinguishable from that of TCMR. Our results argue against a significant value of these biomarkers to reliably distinguish BKPyVAN from rejection.
Topics: Humans; BK Virus; Retrospective Studies; Graft Rejection; Cell-Free Nucleic Acids; Kidney Transplantation; Polyomavirus Infections; Kidney Diseases; Viremia; Antibodies; Biomarkers
PubMed: 35894263
DOI: 10.1111/ctr.14785 -
Journal of Clinical Microbiology Sep 2022Quantitative testing of BK virus (BKPyV) nucleic acid has become the standard of care in transplant patients. While the relationship between interassay harmonization and...
Quantitative testing of BK virus (BKPyV) nucleic acid has become the standard of care in transplant patients. While the relationship between interassay harmonization and commutability has been well characterized for other transplant-related viruses, it has been less well studied for BKPyV, particularly regarding differences in commutability between matrices. Here, interassay agreement was evaluated among six real-time nucleic acid amplification tests (NAATs) and one digital PCR (dPCR) BKPyV assay. Differences in the commutability of three quantitative standards was examined across all assays using a variety of statistical approaches. Panels, including 40 samples each of plasma and urine samples previously positive for BKPyV, together with one previously negative plasma sample and four previously negative urine samples, were tested using all assays, with each real-time NAAT utilizing its usual quantitative calibrators. Serial dilutions of WHO, National Institute for Standards and Technology (NIST), and commercially produced (Exact/Bio-Rad) reference materials were also run by each assay as unknowns. The agreement of the clinical sample values was assessed as a group and in a pairwise manner. The commutability was estimated using both relativistic and quantitative means. The quantitative agreement across assays in the urine samples was within a single log unit across all assays, while the results from the plasma samples varied by 2 to 3 log IU/mL. The commutability showed a similar disparity between the matrices. Recalibration using international standards diminished the resulting discrepancies in some but not all cases. Differences in the sample matrix can affect the commutability and interassay agreement of quantitative BKPyV assays. Differences in commutability between matrices may largely be due to factors other than those such as amplicon size, previously described as important in the case of cytomegalovirus. Continued efforts to standardize viral load measurements must address multiple sources of variability and account for differences in assay systems, quantitative standards, and sample matrices.
Topics: BK Virus; Cytomegalovirus; Humans; Nucleic Acids; Reference Standards; Viral Load
PubMed: 35997500
DOI: 10.1128/jcm.00555-22