Background

Epitope-based tissue matching may be superior to HLA antigen matching. We compared antigen to molecular-level HLA matching on outcomes following pediatric heart transplantation (HTx).

Methods

This is a retrospective, single centre cohort study (2013-2020). HLA antigen and eplet mismatch analyses were performed in HTx patients <18 years old. Primary endpoint was graft loss; secondary endpoints were rejection and cardiac allograft vasculopathy (CAV). A multivariable Cox regression analysis was used to examine associations between eplet or antigen mismatching and outcomes. A logistic regression analysis was performed to examine associations between eplet or antigen mismatching and outcomes.

Results

Seventy-seven patients (40% males) were included, with a median age at HTx 4.3 years [range 0.05-18]. Median HLA class I and II eplet mismatches were 10 (1-22) and 11 (1-23). Median class I and II antigen mismatches were 5 (1-6) and 4 (0-6). 9 patients (11.7%) died [median time 4 months (range 0.1-46)]. Eight (10.4%) patients developed AMR [median time 22 days (IQR = 168)]. Twenty-one patients (27.3%) had acute cellular rejection [median time 40 days (IQR = 85.5)]. In univariate analysis, patients with HLA Class II DPB eplet mismatches above the median for this cohort had an increased risk of graft loss (OR 5.3 [95%CI: 1.03-27.5], p = 0.039). HLA eplet mismatching was not associated with rejection; antigen mismatching was not associated with either graft loss or rejection. In multivariable analysis, patients with HLA Class II DPB eplet mismatches above the median had an increased risk of graft loss (HR 8.14 [95% CI: 1.26-49], p = 0.02). HLA eplet mismatching was not associated with rejection; antigen mismatching was not associated with graft loss or rejection. A logistic regression analysis including 'number of HLA Class II DPB eplet mismatches’ correctly predicted 95.8% of the outcomes.

Conclusion

In our cohort of pediatric heart transplant recipients, the number of HLA Class II DPB eplet mismatches was associated with graft loss. Molecular-level HLA matching is an emerging tool for graft loss risk stratification, but further study is required.

中文翻译：

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小儿心脏移植中的 Eplet 匹配：SickKids 体验

背景

基于表位的组织匹配可能优于 HLA 抗原匹配。我们比较了抗原与分子水平 HLA 匹配对儿科心脏移植 (HTx) 后结果的影响。

方法

这是一项回顾性、单中心队列研究（2013-2020）。在<18 岁的 HTx 患者中进行 HLA 抗原和 eplet 错配分析。主要终点是移植物丢失；次要终点是排斥反应和心脏同种异体移植血管病变（CAV）。多变量Cox 回归分析用于检查 eplet 或抗原不匹配与结果之间的关联。进行逻辑回归分析以检查 eplet 或抗原不匹配与结果之间的关联。

结果

包括 77 名患者（40% 男性），中位年龄为 HTx 4.3 岁 [范围 0.05-18]。中值 HLA I 类和 II 类 eplet 错配为 10 (1-22) 和 11 (1-23)。中值 I 类和 II 类抗原错配为 5 (1-6) 和 4 (0-6)。9 名患者 (11.7%) 死亡 [中位时间 4 个月 (范围 0.1-46)]。八名 (10.4%) 患者出现 AMR [中位时间 22 天 (IQR = 168)]。21 名患者 (27.3%) 出现急性细胞排斥反应 [中位时间 40 天 (IQR = 85.5)]。在单变量分析中，HLA II 类 DPB eplet 错配高于该队列中位数的患者移植物丢失风险增加（OR 5.3 [95%CI: 1.03-27.5]，p = 0.039)。HLA eplet 不匹配与拒绝无关；抗原错配与移植物丢失或排斥无关。在多变量分析中，HLA II 类 DPB eplet 错配高于中位数的患者移植物丢失风险增加（HR 8.14 [95% CI: 1.26-49]，p  = 0.02）。HLA eplet 不匹配与拒绝无关；抗原错配与移植物丢失或排斥无关。包括“HLA II 类 DPB eplet 错配数”在内的逻辑回归分析正确预测了 95.8% 的结果。

结论

在我们的儿科心脏移植受者队列中，HLA II 类 DPB eplet 错配的数量与移植物丢失有关。分子水平的 HLA 匹配是移植物丢失风险分层的新兴工具，但需要进一步研究。