Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA.
Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA, USA.
Transpl Int. 2019 Aug;32(8):831-838. doi: 10.1111/tri.13421. Epub 2019 Apr 2.
Mechanisms of chronic rejection of vascularized composite allografts (VCA) remain poorly understood and likely present along a spectrum of highly varied clinicopathological findings. Across both animal and human VCA however, graft vasculopathy (GV) has been the most consistent pathological finding resulting clinically in irreversible allograft dysfunction and eventual loss. A literature review of all reported clinical VCA cases with documented GV up to December 2018 was thus performed to elucidate the possible mechanisms involved. Relevant data extracted include C4d deposition, donor-specific antibody (DSA) formation, extent of human leukocyte antigen (HLA) mismatch, pretransplant panel reactive antibody levels, induction and maintenance immunosuppression used, the number of preceding acute rejection episodes, and time to histological confirmation of GV. Approximately 6% (13 of 205) of all VCA patients reported to date developed GV at a mean of 6 years post-transplantation. 46% of these patients have either lost or had their VCAs removed. Neither C4d nor DSA alone was predictive of GV development; however, when both are present, VCA loss appears inevitable due to progressive GV. Of utmost concern, GV in VCA does not appear to be abrogated by currently available immunosuppressive treatment and is essentially irreversible by the time of diagnosis with allograft loss a likely eventuality.
血管化复合异体移植物（VCA）慢性排斥的机制仍知之甚少，可能存在于高度变化的临床病理表现谱中。然而，在动物和人类 VCA 中，移植物血管病（GV）一直是最一致的病理发现，导致不可逆转的移植物功能障碍和最终丧失。因此，对截至 2018 年 12 月所有有记录的 GV 的临床 VCA 病例进行了文献回顾，以阐明可能涉及的机制。提取的相关数据包括 C4d 沉积、供体特异性抗体（DSA）形成、人类白细胞抗原（HLA）错配程度、移植前面板反应性抗体水平、使用的诱导和维持免疫抑制、急性排斥反应发作的次数，以及组织学证实 GV 的时间。迄今为止，大约 6%（205 例中的 13 例）的所有 VCA 患者在移植后 6 年平均发生 GV。这些患者中有 46%已经失去或已经移除了他们的 VCA。单独的 C4d 或 DSA 都不能预测 GV 的发展；然而，当两者都存在时，由于进行性 GV，VCA 的丢失似乎是不可避免的。最令人担忧的是，目前可用的免疫抑制治疗似乎并不能阻止 VCA 中的 GV，并且在诊断时 GV 几乎是不可逆转的，移植物丢失是很可能的结果。
