Transplant Institute, NYU Langone Health, New York, NY.
Division of Nephrology, Department of Medicine, NYU Langone Health, New York, NY.
Ann Surg. 2018 Sep;268(3):488-496. doi: 10.1097/SLA.0000000000002924.
The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult.
IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG.
Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant.
All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days.
IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.
由于存在发生超急性排斥反应的风险，供体特异性阳性交叉配型被认为是肾移植的禁忌症。脱敏是去除有害的供体特异性抗体（DSA）的过程，以便安全地进行移植。传统上，这涉及到需要数天至数周进行的血浆置换和静脉注射免疫球蛋白治疗，并且当有活体供体且移植日期已知时，这种方法是可行的，这为抢先治疗提供了时间。对于没有活体供体的致敏患者，历史上移植一直很困难。
IdeS（依利西单抗）是一种来源于酿脓链球菌的内肽酶，对人 IgG 具有特异性，静脉内输注会导致 IgG 迅速裂解。
在这里，我们介绍了我们单中心的经验，共有 7 名高度致敏（cPRA98-100%）的肾移植候选者，他们的供体（5 名已故，2 名活体）的 DSA 导致与供体的交叉配型呈阳性，这些患者在移植前 24 小时内接受了 IdeS 治疗。
所有预 IdeS 交叉配型均为阳性，否则将禁止进行移植。所有交叉配型在 IdeS 治疗后均转为阴性，患者成功进行了移植。3 名患者出现 DSA 反弹和抗体介导的排斥反应，经标准治疗后得到缓解。3 名患者出现延迟移植物功能，最终得到解决。没有与 IdeS 相关的严重不良事件。所有患者的移植肾功能均正常，中位随访时间为 235 天。
IdeS 可能为那些否则可能没有希望接受挽救生命的移植的患者提供了一种开创性的新脱敏方法。
