Edwards Jonathan J, Seliktar Naomi, White Rachel, Heron Steven D, Lin Kimberly, Rossano Joseph, Monos Dimitri, Sesok-Pizzini Deborah, O'Connor Matthew J
Department of Pediatrics, Division of Pediatric Cardiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Technion Israel Institute of Technology, Haifa, Israel.
J Heart Lung Transplant. 2019 Nov;38(11):1206-1213. doi: 10.1016/j.healun.2019.08.018. Epub 2019 Aug 25.
Desensitization, the process of reducing anti-human leukocyte antigen (HLA) antibodies in sensitized patients awaiting heart transplantation (HT), has unclear efficacy in pediatric HT candidates.
Pediatric HT candidates listed at our institution between January 1, 2013 and June 30, 2018 were retrospectively evaluated. Sensitization was defined as the calculated panel reactive antibody (cPRA) ≥ 10% with ≥ 1 a strong positive antibody. The desensitization response was defined as a ≥ 25% reduction in the mean fluorescence intensity (MFI) for ≥ 90% of the strong positive antibodies on follow-up panel reactive antibody (PRA) testing before waitlist removal, HT, or death (data available for 13 patients).
The HT candidates were categorized as sensitized receiving desensitization therapy (ST, n = 14), sensitized not receiving therapy (SNT, n = 18), or non-sensitized (n = 55). A desensitization response was observed in 8 (62%) of the ST upon repeat PRA testing, with the ST responders receiving more doses of intravenous immunoglobulin (IVIG) (8 vs 2, p < 0.05). The anti-HLA class I antibodies were particularly resistant for non-responders (p = 1.9 × 10). The combination of homograft and ventricular assist device was more sensitizing than either alone (p = 3.1 × 10). However, these sensitization risk factors did not impact the desensitization response. The ST was associated with a higher likelihood of remaining listed and a longer waitlist time without substantially impacting the HT rate, waitlist mortality, or early post-HT outcomes.
Most ST patients had a favorable response to desensitization, with a dose-dependent response observed for IVIG. The anti-HLA class likely impacts the ST response, whereas traditional sensitization risk factors had no impact on the response.
脱敏是指在等待心脏移植（HT）的致敏患者中降低抗人类白细胞抗原（HLA）抗体的过程，其在儿科HT候选者中的疗效尚不清楚。
对2013年1月1日至2018年6月30日在本机构登记的儿科HT候选者进行回顾性评估。致敏定义为计算得出的群体反应性抗体（cPRA）≥10%且至少有1种强阳性抗体。脱敏反应定义为在等待名单移除、HT或死亡前的随访群体反应性抗体（PRA）检测中，≥90%的强阳性抗体的平均荧光强度（MFI）降低≥25%（13例患者有可用数据）。
HT候选者被分为接受脱敏治疗的致敏患者（ST，n = 14）、未接受治疗的致敏患者（SNT，n = 18）或非致敏患者（n = 55）。重复PRA检测时，8例（62%）ST患者出现脱敏反应，ST反应者接受了更多剂量的静脉注射免疫球蛋白（IVIG）（8剂 vs 2剂，p < 0.05）。抗HLA I类抗体对无反应者尤其具有抗性（p = 1.9×10）。同种移植和心室辅助装置联合使用比单独使用更具致敏性（p = 3.1×10）。然而，这些致敏风险因素并未影响脱敏反应。ST与留在等待名单上的可能性更高以及等待名单时间更长相关，而对HT率、等待名单死亡率或HT后早期结局没有实质性影响。
大多数ST患者对脱敏有良好反应，观察到IVIG有剂量依赖性反应。抗HLA类别可能影响ST反应，而传统的致敏风险因素对反应没有影响。
