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

Frontiers in Pediatrics

article

Olga Charnaya¹  Daniella Levy Erez²  Sandra Amaral³  Dimitrios S. Monos⁴ 

[1] Department of Pediatrics, Johns Hopkins University School of Medicine;Schneider Children's Medical Center, Institute of Pediatric Nephrology;Departments of Pediatric Nephrology and Biostatistics, Epidemiology and Informatics, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania;Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania

关键词: kidney transplant;    epitope;    eplet;    pediatric;    donor specific antibodies;   

DOI  :  10.3389/fped.2022.893002

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY