Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching
Kidney transplant is the optimal treatment for end-stage kidney disease as it offers significant survival and quality of life advantages over dialysis. While recent advances have significantly improved early graft outcomes, long-term overall graft survival has remained largely unchanged for the last...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2022.893002/full |
| _version_ | 1811336212178272256 |
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| author | Olga Charnaya Daniella Levy Erez Daniella Levy Erez Sandra Amaral Dimitrios S. Monos |
| author_facet | Olga Charnaya Daniella Levy Erez Daniella Levy Erez Sandra Amaral Dimitrios S. Monos |
| author_sort | Olga Charnaya |
| collection | DOAJ |
| description | Kidney transplant is the optimal treatment for end-stage kidney disease as it offers significant survival and quality of life advantages over dialysis. While recent advances have significantly improved early graft outcomes, long-term overall graft survival has remained largely unchanged for the last 20 years. Due to the young age at which children receive their first transplant, most children will require multiple transplants during their lifetime. Each subsequent transplant becomes more difficult because of the development of de novo donor specific HLA antibodies (dnDSA), thereby limiting the donor pool and increasing mortality and morbidity due to longer time on dialysis awaiting re-transplantation. Secondary prevention of dnDSA through increased post-transplant immunosuppression in children is constrained by a significant risk for viral and oncologic complications. There are currently no FDA-approved therapies that can meaningfully reduce dnDSA burden or improve long-term allograft outcomes. Therefore, primary prevention strategies aimed at reducing the risk of dnDSA formation would allow for the best possible long-term allograft outcomes without the adverse complications associated with over-immunosuppression. Epitope matching, which provides a more nuanced assessment of immunological compatibility between donor and recipient, offers the potential for improved donor selection. Although epitope matching is promising, it has not yet been readily applied in the clinical setting. Our review will describe current strengths and limitations of epitope matching software, the evidence for and against improved outcomes with epitope matching, discussion of eplet load vs. variable immunogenicity, and conclude with a discussion of the delicate balance of improving matching without disadvantaging certain populations. |
| first_indexed | 2024-04-13T17:36:13Z |
| format | Article |
| id | doaj.art-84bb21d90e704f6093eb506b0a341911 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-04-13T17:36:13Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-84bb21d90e704f6093eb506b0a3419112022-12-22T02:37:22ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602022-06-011010.3389/fped.2022.893002893002Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet MatchingOlga Charnaya0Daniella Levy Erez1Daniella Levy Erez2Sandra Amaral3Dimitrios S. Monos4Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesSchneider Children's Medical Center, Institute of Pediatric Nephrology, Petah Tikvah, IsraelDepartments of Pediatric Nephrology and Biostatistics, Epidemiology and Informatics, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartments of Pediatric Nephrology and Biostatistics, Epidemiology and Informatics, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesKidney transplant is the optimal treatment for end-stage kidney disease as it offers significant survival and quality of life advantages over dialysis. While recent advances have significantly improved early graft outcomes, long-term overall graft survival has remained largely unchanged for the last 20 years. Due to the young age at which children receive their first transplant, most children will require multiple transplants during their lifetime. Each subsequent transplant becomes more difficult because of the development of de novo donor specific HLA antibodies (dnDSA), thereby limiting the donor pool and increasing mortality and morbidity due to longer time on dialysis awaiting re-transplantation. Secondary prevention of dnDSA through increased post-transplant immunosuppression in children is constrained by a significant risk for viral and oncologic complications. There are currently no FDA-approved therapies that can meaningfully reduce dnDSA burden or improve long-term allograft outcomes. Therefore, primary prevention strategies aimed at reducing the risk of dnDSA formation would allow for the best possible long-term allograft outcomes without the adverse complications associated with over-immunosuppression. Epitope matching, which provides a more nuanced assessment of immunological compatibility between donor and recipient, offers the potential for improved donor selection. Although epitope matching is promising, it has not yet been readily applied in the clinical setting. Our review will describe current strengths and limitations of epitope matching software, the evidence for and against improved outcomes with epitope matching, discussion of eplet load vs. variable immunogenicity, and conclude with a discussion of the delicate balance of improving matching without disadvantaging certain populations.https://www.frontiersin.org/articles/10.3389/fped.2022.893002/fullkidney transplantepitopeepletpediatricdonor specific antibodies |
| spellingShingle | Olga Charnaya Daniella Levy Erez Daniella Levy Erez Sandra Amaral Dimitrios S. Monos Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching Frontiers in Pediatrics kidney transplant epitope eplet pediatric donor specific antibodies |
| title | Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching |
| title_full | Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching |
| title_fullStr | Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching |
| title_full_unstemmed | Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching |
| title_short | Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching |
| title_sort | pediatric kidney transplantation can we do better the promise and limitations of epitope eplet matching |
| topic | kidney transplant epitope eplet pediatric donor specific antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fped.2022.893002/full |
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