Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody-Mediated Rejection
Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody-Mediated Rejection
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DOI：
10.1111/ajt.13529
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发表时间：
2016-01-01
影响因子：
8.8
通讯作者：
Huyen, J. P. Duong Van
中科院分区：
文献类型：
--
作者：
Loupy, A.;Toquet, C.;Huyen, J. P. Duong Van
在心脏移植中，缺乏强有力的证据来证明晚期同种异体移植失败的具体原因。我们假设大部分同种异体心脏移植失败可能与抗体介导的损伤和免疫介导的冠状动脉硬化有关。我们纳入了在三个转诊中心因晚期晚期同种异体心脏移植衰竭而接受再移植的所有患者。我们通过评估心脏血管树（包括组织病理学和免疫组织化学以及循环供体特异性抗体）来执行心脏同种异体移植表型的综合策略。主要分析包括 40 名同种异体心脏移植患者和 402 名同种异体移植丢失前进行的心内膜心肌活检。总体而言，在 19 例 (47.5%) 失败的同种异体心脏移植物中观察到抗体介导的排斥反应，其中 16 名患者 (40%) 在同种异体移植物丧失之前 4.5 +/- 3.5 年发生了未识别的亚临床抗体介导的排斥反应。与没有抗体介导排斥反应的外植同种异体移植物（0.42 +/- 0.11 和 0.36 +/- 0.09，p = 0.046 和 p < 0.0001，分别）。在纯冠状动脉硬化和混合（动脉硬化和动脉粥样硬化）模式的失败同种异体移植物中，62.1% 观察到抗体介导的损伤，而在纯冠状动脉粥样硬化患者中未观察到抗体介导的损伤（p = 0.0076）。我们证明抗体介导的排斥反应在大部分衰竭的同种异体心脏移植物中起作用，并且与严重的冠状动脉硬化有关。未识别的亚临床抗体介导的排斥反应可能在同种异体移植失败前几年就观察到。
In heart transplantation, there is a lack of robust evidence of the specific causes of late allograft failure. We hypothesized that a substantial fraction of failing heart allografts may be associated with antibody-mediated injury and immune-mediated coronary arteriosclerosis. We included all patients undergoing a retransplantation for late terminal heart allograft failure in three referral centers. We performed an integrative strategy of heart allograft phenotyping by assessing the heart vascular tree including histopathology and immunohistochemistry together with circulating donor-specific antibodies. The main analysis included 40 explanted heart allografts patients and 402 endomyocardial biopsies performed before allograft loss. Overall, antibody-mediated rejection was observed in 19 ( 47.5%) failing heart allografts including 16 patients (40%) in whom unrecognized previous episodes of subclinical antibody-mediated rejection occurred 4.5 +/- 3.5 years before allograft loss. Explanted allografts with evidence of antibody-mediated rejection demonstrated higher endothelitis and microvascular inflammation scores (0.89 +/- 0.26 and 2.25 +/- 0.28, respec-tively) compared with explanted allografts without antibody-mediated rejection (0.42 +/- 0.11 and 0.36 +/- 0.09, p = 0.046 and p < 0.0001, respectively). Antibody-mediated injury was observed in 62.1% of failing allografts with pure coronary arteriosclerosis and mixed (arteriosclerosis and atherosclerosis) pattern, while it was not observed in patients with pure coronary atherosclerosis (p = 0.0076). We demonstrate that antibody-mediated rejection is operating in a substantial fraction of failing heart allografts and is associated with severe coronary arteriosclerosis. Unrecognized subclinical antibody-mediated rejection episodes may be observed years before allograft failure.