Labatt Family Heart Centre - The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada; Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
J Heart Lung Transplant. 2022 Oct;41(10):1470-1477. doi: 10.1016/j.healun.2022.06.023. Epub 2022 Jul 5.
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).
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.
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.
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.
基于表位的组织配型可能优于 HLA 抗原配型。我们比较了儿科心脏移植（HTx）后抗原与分子水平 HLA 配型的结果。
这是一项回顾性、单中心队列研究（2013-2020 年）。对<18 岁的 HTx 患者进行 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（CAV）。使用多变量 Cox 回归分析检查 eplet 或抗原错配与结局之间的关系。使用逻辑回归分析检查 eplet 或抗原错配与结局之间的关系。
共纳入 77 例患者（40%为男性），HTx 时的中位年龄为 4.3 岁[范围 0.05-18]。中位 HLA Ⅰ类和Ⅱ类 eplet 错配分别为 10（1-22）和 11（1-23）。中位Ⅰ类和Ⅱ类抗原错配分别为 5（1-6）和 4（0-6）。9 例（11.7%）患者死亡[中位时间 4 个月（范围 0.1-46）]。8 例（10.4%）患者发生 AMR[中位时间 22 天（IQR=168）]。21 例（27.3%）患者发生急性细胞排斥反应[中位时间 40 天（IQR=85.5）]。在单变量分析中，HLA Ⅱ类 DPB eplet 错配高于本队列中位数的患者，移植物丢失风险增加（OR 5.3[95%CI：1.03-27.5]，p=0.039）。HLA eplet 错配与排斥反应无关；抗原错配与移植物丢失或排斥反应无关。多变量分析中，HLA Ⅱ类 DPB eplet 错配高于本队列中位数的患者，移植物丢失风险增加（HR 8.14[95%CI：1.26-49]，p=0.02）。HLA eplet 错配与排斥反应无关；抗原错配与移植物丢失或排斥反应无关。包括“HLA Ⅱ类 DPB eplet 错配数量”的逻辑回归分析正确预测了 95.8%的结果。
在我们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 HLA 配型是一种新兴的移植物丢失风险分层工具，但需要进一步研究。
