Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Curr Opin Immunol. 2009 Oct;21(5):569-72. doi: 10.1016/j.coi.2009.07.010. Epub 2009 Aug 12.
One of the major challenges in the current era of organ transplantation is to find suitable organs for highly sensitized patients. Different approaches have been successful in a proportion of the patients. Several organ exchange organizations are currently implementing an acceptable mismatch program similar to the one developed by Eurotransplant. The basis of such a program is the accurate definition of those HLA antigens or epitopes toward which the patient did not form antibodies. Donors, who are compatible with the combination of the HLA type of the recipient and these acceptable HLA mismatches, will have a negative crossmatch and are allocated with the highest priority to the highly sensitized patient. Such an approach has shown to increase the transplantation rate with excellent results. Another possibility to find a crossmatch negative donor for highly sensitized patients, who have a positive crossmatch with their potential living donor, is via a (national) paired kidney exchange program. Alternative approaches aim at desensitization of the patient in order to be able to transplant the patient with a donor despite the original crossmatch was positive. Recent protocols include the use of intravenous immunoglobulin in combination with an anti CD20 monoclonal antibody (Rituximab). In order to eliminate the antibody producing plasma cells as well, Bortezomib is recently proposed as a possible agent for future desensitization protocols. As none of these approaches are successful in all patients, a comprehensive use of a combination of these strategies seems the way to go.
当前器官移植领域面临的主要挑战之一是为高致敏患者寻找合适的器官。不同的方法在一部分患者中取得了成功。目前，一些器官交换组织正在实施一个可接受的错配方案，类似于欧洲移植组织开发的方案。该方案的基础是准确定义患者未形成抗体的那些 HLA 抗原或表位。与受者 HLA 类型和这些可接受的 HLA 错配相匹配的供者将具有阴性交叉配型，并被分配给高度致敏的患者，优先级最高。这种方法已被证明可以提高移植率，并取得了优异的效果。对于与潜在活体供者的交叉配型呈阳性的高度致敏患者，另一种找到交叉配型阴性供者的方法是通过（国家）配对肾脏交换计划。替代方法旨在使患者脱敏，以便能够在原始交叉配型呈阳性的情况下将患者与供者进行移植。最近的方案包括使用静脉注射免疫球蛋白与抗 CD20 单克隆抗体（利妥昔单抗）联合使用。为了消除产生抗体的浆细胞，硼替佐米最近被提议作为未来脱敏方案的一种可能药物。由于这些方法都不能在所有患者中成功，因此似乎需要综合使用这些策略的组合。
