Amore Alessandro
Department of Nephrology, Regina Margherita University Hospital, Azienda Ospedaliera Universitaria, Città della Salute e della Scienza, Torino, Italy.
Curr Opin Organ Transplant. 2015 Oct;20(5):536-42. doi: 10.1097/MOT.0000000000000230.
Over the last five decades, the attention of nephrologists has focused on cellular rejection which was considered to be responsible for the early loss of function of the transplanted kidney. The use of new drugs in different combinations with steroids resulted in an improved short-term survival of the graft, which has significantly reduced the incidence of acute rejections. The main problem now, however, is ensuring the long-term survival of the transplanted kidney. This has become the challenge of the new millennium.
The current literature clearly focuses on donor-specific alloantibodies, directed against human leukocyte antigen (HLA) and non-HLA antigens [donor-specific antibodies (DSA)], which have been shown to play an important role in graft dysfunction, longevity, and loss. To mitigate allograft loss due to antibodies, it is important to treat the source of antibody production, the plasma cells. Drugs used prior to 2007, such as Rituximab, intravenous immunoglobulins, and plasmapheresis, lack effects on these long-lived plasma cells. Their ability to remove DSA is incomplete and/or cost prohibitive. Since 2007, Bortezomib, a proteasome inhibitor, has been used to deplete plasma cells, thus eliminating the synthesis of DSA.
Antibody-mediated rejection (AMR) is common in patients with DSA and is associated with a poor prognosis. Novel medications that target each step of AMR pathogenesis have been produced and are successful when compared with more traditional therapies.
在过去的五十年里，肾脏病学家的注意力集中在细胞性排斥反应上，这种反应被认为是导致移植肾早期功能丧失的原因。不同药物与类固醇联合使用提高了移植物的短期存活率，显著降低了急性排斥反应的发生率。然而，现在的主要问题是确保移植肾的长期存活。这已成为新千年的挑战。
当前文献明确聚焦于针对人类白细胞抗原（HLA）和非HLA抗原的供体特异性同种抗体[供体特异性抗体（DSA）]，这些抗体已被证明在移植物功能障碍、寿命和丢失方面起重要作用。为减轻抗体导致的同种异体移植物丢失，治疗抗体产生的源头即浆细胞很重要。2007年之前使用的药物，如利妥昔单抗、静脉注射免疫球蛋白和血浆置换，对这些长寿浆细胞缺乏作用。它们清除DSA的能力不完整和/或成本过高。自2007年以来，蛋白酶体抑制剂硼替佐米已被用于清除浆细胞，从而消除DSA的合成。
抗体介导的排斥反应（AMR）在DSA患者中很常见，且预后不良。与更传统的疗法相比，针对AMR发病机制每个环节的新型药物已经问世并取得了成功。
