Perfusion Department, Great Ormond Street Hospital for Children, London, UK.
Institute of Cardiovascular Science, University College London, London, UK.
Perfusion. 2024 Apr;39(3):543-554. doi: 10.1177/02676591221151035. Epub 2023 Jan 10.
Anti-human leukocyte antigen (HLA)-antibody production represents a major barrier to heart transplantation, limiting recipient compatibility with potential donors and increasing the risk of complications with poor waiting-list outcomes. Currently there is no consensus to when desensitization should take place, and through what mechanism, meaning that sensitized patients must wait for a compatible donor for many months, if not years. We aimed to determine if intraoperative immunoadsorption could provide a potential desensitization methodology.
Anti-HLA antibody-containing whole blood was added to a Cardiopulmonary bypass (CPB) circuit set up to mimic a 20 kg patient undergoing heart transplantation. Plasma was separated and diverted to a standalone, secondary immunoadsorption system, with antibody-depleted plasma returned to the CPB circuit. Samples for anti-HLA antibody definition were taken at baseline, when combined with the CPB prime (on bypass), and then every 20 min for the duration of treatment (total 180 min).
A reduction in individual allele median fluorescence intensity (MFI) to below clinically relevant levels (<1000 MFI), and in the majority of cases below the lower positive detection limit (<500 MFI), even in alleles with a baseline MFI >4000 was demonstrated. Reduction occurred in all cases within 120 min, demonstrating efficacy in a time period usual for heart transplantation. Flowcytometric crossmatching of suitable pseudo-donor lymphocytes demonstrated a change from T cell and B cell positive channel shifts to negative, demonstrating a reduction in binding capacity.
Intraoperative immunoadsorption in an setting demonstrates clinically relevant reductions in anti-HLA antibodies within the normal timeframe for heart transplantation. This method represents a potential desensitization technique that could enable sensitized children to accept a donor organ earlier, even in the presence of donor-specific anti-HLA antibodies.
抗人白细胞抗原 (HLA）-抗体的产生是心脏移植的主要障碍，限制了受者与潜在供者的相容性，并增加了因等待名单结果不佳而出现并发症的风险。目前，对于何时应进行脱敏以及通过何种机制进行脱敏，尚无共识，这意味着致敏患者必须等待数月甚至数年才能找到合适的供体。我们旨在确定术中免疫吸附是否可以提供一种潜在的脱敏方法。
将含有抗 HLA 抗体的全血加入到一个心肺旁路 (CPB) 回路中，该回路模拟 20 公斤的患者进行心脏移植。将血浆分离并转移到一个独立的、辅助免疫吸附系统中，将抗体耗尽的血浆返回 CPB 回路。在基线时、与 CPB 初始值（在体外循环时）结合时以及治疗期间（总共 180 分钟）的每 20 分钟取一次样本，以确定抗 HLA 抗体的定义。
显示个体等位基因中位荧光强度 (MFI）降低到临床相关水平（<1000 MFI）以下，在大多数情况下降低到较低的阳性检测下限（<500 MFI）以下，甚至在基线 MFI >4000 的等位基因中也是如此。在 120 分钟内，所有病例均显示出减少，证明在心脏移植的通常时间内具有疗效。合适的拟供体淋巴细胞的流式细胞术交叉配型显示 T 细胞和 B 细胞阳性通道的变化从阳性变为阴性，表明结合能力降低。
在心脏移植的正常时间范围内，CPB 环境中的术中免疫吸附可使抗 HLA 抗体产生临床相关降低。这种方法代表了一种潜在的脱敏技术，即使存在供体特异性抗 HLA 抗体，也可以使致敏儿童更早地接受供体器官。
