Mangiola Massimo, Marrari Marilyn, Xu Qingyong, Sanchez Pablo G, Zeevi Adriana
NYU Langone Transplant Institute, New York, NY, USA.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
J Thorac Dis. 2021 Nov;13(11):6725-6736. doi: 10.21037/jtd-2021-21.
The presence of HLA antibodies is widely recognized as a barrier to solid organ transplantation, and for lung transplant candidates, it has a significant negative impact on both waiting time and waiting list mortality. Although HLA antibodies have been associated with a broad spectrum of allograft damage, precise characterization of these antibodies in allosensitized candidates may enhance their accessibility to transplant. The introduction of Luminex-based single antigen bead (SAB) assays has significantly improved antibody detection sensitivity and specificity, but SAB alone is not sufficient for risk-stratification. Functional characterization of donor-specific antibodies (DSA) is paramount to increase donor accessibility for allosensitized lung candidates. We describe here our approach to evaluate sensitized lung transplant candidates. By employing state-of-the-art technologies to assess histocompatibility and determine physiological properties of circulating HLA antibodies, we can provide our Clinical Team a better risk assessment for lung transplant candidates and facilitate a "road map" to transplant. The cases presented in this paper illustrate the "individualized steps" taken to determine calculated panel reactive antibodies (cPRA), titer and complement-fixing properties of each HLA antibody present in circulation. When a donor is considered, we can better predict the risk associated with potentially crossing HLA antibodies, thereby allowing the Clinical Team to approach allosensitized lung patients with an individualized medicine approach. To facilitate safe access of sensitized lung transplant candidates to potential donors, a synergy between the histocompatibility laboratory and the Clinical Team is essential. Ultimately, donor acceptance is a decision based on several parameters, leading to a risk-stratification unique for each patient.
HLA抗体的存在被广泛认为是实体器官移植的一个障碍,对于肺移植候选者而言,它对等待时间和等待名单上的死亡率均有显著负面影响。尽管HLA抗体与广泛的同种异体移植物损伤相关,但在致敏候选者中对这些抗体进行精确表征可能会增加他们获得移植的机会。基于Luminex的单抗原珠(SAB)检测方法的引入显著提高了抗体检测的灵敏度和特异性,但仅靠SAB不足以进行风险分层。供体特异性抗体(DSA)的功能表征对于增加致敏肺移植候选者获得供体的机会至关重要。我们在此描述我们评估致敏肺移植候选者的方法。通过采用最先进的技术来评估组织相容性并确定循环中HLA抗体的生理特性,我们能够为临床团队提供关于肺移植候选者更好的风险评估,并为移植制定一个“路线图”。本文所展示的病例说明了为确定循环中存在的每种HLA抗体的计算群体反应性抗体(cPRA)、滴度和补体固定特性而采取的“个体化步骤”。当考虑一个供体时,我们能够更好地预测与潜在交叉HLA抗体相关的风险,从而使临床团队能够以个体化医疗方法来处理致敏肺移植患者。为便于致敏肺移植候选者安全地接触潜在供体,组织相容性实验室与临床团队之间的协同作用至关重要。最终,供体接受是基于多个参数的决定,导致每个患者都有独特的风险分层。