Late Antibody-Mediated Rejection After Heart Transplantation Following the Development of De Novo Donor-Specific Human Leukocyte Antigen Antibody
Late Antibody-Mediated Rejection After Heart Transplantation Following the Development of De Novo Donor-Specific Human Leukocyte Antigen Antibody
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DOI：
10.1097/tp.0b013e318244f7b8
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发表时间：
2012-03-27
期刊：
影响因子：
6.2
通讯作者：
Banner, Nicholas R.
中科院分区：
文献类型：
--
作者：
Hodges, Aidan M.;Lyster, Haifa;Banner, Nicholas R.
背景抗体介导的排斥反应（Antibody-mediated rejection，AMR）是心脏移植术后的重要问题。大多数情况下，似乎发生在致敏的受者与预先供者特异性人类白细胞抗原抗体（DSA）移植后早期。在形成新发DSA的患者中，关于AMR的数据很少。我们描述了继发于新发DSA的晚期AMR的临床特征和治疗结果。这是一项回顾性、观察性队列研究。所有2005年11月至2011年8月间因继发于新发DSA的症状性AMR接受心脏移植的患者。15例患者接受AMR治疗，发生率为3.1例/1000人年，患病率为1.4%。所有患者就诊时均有心力衰竭证据，诊断时进行了新发DSA检查。有一系列的组织学和免疫组化结果。尽管采用免疫分离、静脉注射免疫球蛋白和利妥昔单抗治疗，在某些情况下采用全淋巴结照射（n = 3）和硼替佐米（n = 2）治疗，但临床结局较差。使用Labscreen单抗原试剂盒测量的DSA抗体水平平均降低76%，中位数为77%，范围为35%至99%，但未消除。46%的患者有持续的心脏移植物功能障碍。AMR诊断后的平均和中位生存期分别为1.3年和0.8年。在研究期结束时，只有40%的人活着。原发性DSA引起的晚期心脏AMR是一种罕见但严重的问题。尽管治疗符合目前的最佳实践，但46%的患者发生持续性心功能不全，中期生存率很低。
Background. Antibody-mediated rejection (AMR) is an important problem after heart transplantation. Most cases seem to occur in sensitized recipients with preformed donor-specific human leukocyte antigen antibody (DSA) early after transplantation. Few data exist on AMR in patients who form de novo DSA. We describe the clinical features and treatment outcome for late AMR secondary to de novo DSA.Methods. This was a retrospective, observational cohort study. All heart transplant patients treated for symptomatic AMR secondary to de novo DSA between November 2005 and August 2011.Results. Fifteen patients were treated for AMR giving an incidence of 3.1 cases per 1000 person years and a prevalence of 1.4%. All had evidence of heart failure on presentation and de novo DSA at diagnosis. There was a spectrum of histologic and immunohistochemical findings. Despite treatment with immunepheresis, intravenous immunoglobulin, and rituximab, and in some cases total lymph node irradiation (n = 3) and bortezomib (n = 2), clinical outcomes were poor. DSA antibody levels, measured using Labscreen single antigen kits, were reduced by a mean of 76% with a median of 77% and a range of 35% to 99%, but were not eliminated. Forty-six percent had persistent cardiac allograft dysfunction. Mean and median survival was 1.3 and 0.8 years after diagnosis of AMR. Only 40% were alive at the end of the study period.Conclusion. Late cardiac AMR caused by de novo DSA was an uncommon but serious problem. Despite treatment consistent with current best practice, 46% of patients developed persistent cardiac dysfunction and their medium-term survival was poor.