Introduction

Presence of donor-specific antibodies (DSAs), particularly to class II antigens, remains a major challenge in pediatric heart transplantation. Donor-recipient human leukocyte antigen (HLA) matching is a potential strategy to mitigate poor outcomes associated with DSAs. We evaluated the hypothesis that antigen mismatching at the DQB1 locus is associated with worse rejection-free survival.

Methods

Data was collected from Scientific Registry of Transplant Recipients for all pediatric heart transplant recipients 2010-2021. Only transplants with complete HLA typing at the DQB1 locus for recipient and donor were included. Primary outcome was rejection-free graft survival through 5 years.

Results

Of 5,115 children, 4,135 had complete DQB1 typing and were included. Of those, 503 (12%) had 0 DQB1 donor-recipient mismatches, 2,203 (53%) had 1, and 1,429 (35%) had 2. Rejection-free survival through 5 years trended higher for children with 0 DQB1 mismatches (68%), compared to those with 1 (62%) or 2 (63%) mismatches (pairwise p=0.08 for both). In multivariable analysis, 0 DQB1 mismatches remained significantly associated with improved rejection-free graft survival compared to 2 mismatches, while 1 DQB1 mismatch was not. Subgroup analysis showed the strongest effect in non-Hispanic Black children and those undergoing retransplant.

Conclusion

Matching at the DQB1 locus is associated with improved rejection-free survival after pediatric heart transplant, particularly in Black children, and those undergoing retransplant. Assessing high-resolution donor typing at the time of allocation may further corroborate and refine this association. DQB1 matching may improve long-term outcomes in children stabilized either with optimal pharmacotherapy or supported with durable devices able to await ideal donors.

中文翻译：

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DQB1 抗原匹配可提高儿童心脏移植受者的无排斥生存率

介绍

供者特异性抗体（DSA）的存在，特别是针对 II 类抗原的抗体，仍然是儿科心脏移植中的一个主要挑战。供体-受体人类白细胞抗原 (HLA) 匹配是减轻与 DSA 相关的不良结果的潜在策略。我们评估了 DQB1 基因座抗原不匹配与较差的无排斥生存相关的假设。

方法

数据收集自 2010-2021 年所有儿童心脏移植受者的移植受者科学登记处。仅包括受者和供者 DQB1 位点具有完整 HLA 分型的移植物。主要结果是移植物存活 5 年，无排斥反应。

结果

在 5,115 名儿童中，有 4,135 名完成了 DQB1 打字并被纳入其中。其中，503 名（12%）有 0 次 DQB1 供体-受体不匹配，2,203 名（53%）有 1 次，1,429 名（35%）有 2 次。对于 0 次 DQB1 不匹配的儿童，5 年无排斥生存率较高（68 %)，与有 1 个 (62%) 或 2 个 (63%) 错配的样本相比（两者均成对 p=0.08）。在多变量分析中，与 2 个错配相比，0 个 DQB1 错配仍然与改善的无排斥移植物存活率显着相关，而 1 个 DQB1 错配则不然。亚组分析显示，对非西班牙裔黑人儿童和接受再移植的儿童的影响最强。

结论

DQB1 基因座的匹配与儿科心脏移植后无排斥反应生存率的提高相关，特别是黑人儿童和接受再移植的儿童。在分配时评估高分辨率供体分型可能会进一步证实和完善这种关联。DQB1 匹配可以改善通过最佳药物治疗或通过能够等待理想捐赠者的耐用设备支持稳定的儿童的长期结果。