Pediatric Kidney Transplantation—Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching

Olga Charnaya*, Daniella Levy Erez, Sandra Amaral, Dimitrios S. Monos

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Article number893002
JournalFrontiers in Pediatrics
Volume10
DOIs
StatePublished - 3 Jun 2022
Externally publishedYes

Funding

FundersFunder number
Johns Hopkins Institute for Clinical and Translational Research
Center for Africana Studies, Johns Hopkins University
Institute for Clinical and Translational Research, University of Wisconsin, Madison
Johns Hopkins University
Johns Hopkins Bloomberg School of Public Health
Brain Science Institute, Johns Hopkins University
Global Obesity Prevention Center, Johns Hopkins University
Sidney Kimmel Comprehensive Cancer Center
Environment, Energy, Sustainability and Health Institute, Johns Hopkins University
School of Medicine, Johns Hopkins University
Center for Innovative Medicine, Johns Hopkins University
Robert Packard Center for ALS Research, Johns Hopkins University
Applied Physics Laboratory, Johns Hopkins University
Arthritis Center, Johns Hopkins University
Office of the Provost, Johns Hopkins University
Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
Stanley Neurovirology Laboratory, Johns Hopkins University
Whiting School of Engineering, Johns Hopkins University
School of Nursing, Johns Hopkins University
Department of Neurology and Neurosurgery, Johns Hopkins University
Department of Pathology, Johns Hopkins University
Department of Surgery, School of Medicine, Johns Hopkins University
Center for AIDS Research, Johns Hopkins University
Human Language Technology Center of Excellence, Johns Hopkins University
Carey Business School, Johns Hopkins University

    Keywords

    • donor specific antibodies
    • epitope
    • eplet
    • kidney transplant
    • pediatric

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