Charnaya Olga, Levy Erez Daniella, Amaral Sandra, Monos Dimitrios S
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Schneider Children's Medical Center, Institute of Pediatric Nephrology, Petah Tikvah, Israel.
Front Pediatr. 2022 Jun 3;10:893002. doi: 10.3389/fped.2022.893002. eCollection 2022.
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 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.
肾移植是终末期肾病的最佳治疗方法，因为与透析相比，它在生存率和生活质量方面具有显著优势。虽然最近的进展显著改善了早期移植肾的预后，但在过去20年中，移植肾的长期总体生存率基本保持不变。由于儿童首次接受移植时年龄较小，大多数儿童在其一生中需要多次移植。由于供体特异性HLA抗体（dnDSA）的产生，每一次后续移植都变得更加困难，从而限制了供体库，并因等待再次移植的透析时间延长而增加了死亡率和发病率。通过增加儿童移植后的免疫抑制来对dnDSA进行二级预防受到病毒和肿瘤并发症重大风险的限制。目前尚无FDA批准的疗法能够有效降低dnDSA负担或改善移植肾的长期预后。因此，旨在降低dnDSA形成风险的一级预防策略将实现最佳的移植肾长期预后，同时避免过度免疫抑制带来的不良并发症。表位匹配能够更细致地评估供体和受体之间的免疫相容性，为改进供体选择提供了可能。尽管表位匹配前景广阔，但尚未在临床中得到广泛应用。我们的综述将描述表位匹配软件目前的优势和局限性、支持和反对表位匹配改善预后的证据、表位负荷与可变免疫原性的讨论，并以在不使某些人群处于不利地位的情况下改善匹配的微妙平衡的讨论作为结论。
