Jaffe Ian S, Runström Anna, Tatapudi Vasishta S, Weldon Elaina P, Deterville Cecilia L, Dieter Rebecca A, Montgomery Robert A, Lonze Bonnie E, Mangiola Massimo
Department of Surgery, New York University Grossman School of Medicine, New York, NY.
New York University Langone Transplant Institute, New York, NY.
Transplant Direct. 2025 Jan 9;11(2):e1752. doi: 10.1097/TXD.0000000000001752. eCollection 2025 Feb.
Imlifidase is an IgG-cleaving endopeptidase conditionally approved in Europe for desensitization of highly sensitized patients before kidney transplantation. We present 5-y outcomes and donor-specific antibody (DSA) levels for clinical trial participants from a single site who received imlifidase for desensitization before incompatible transplantation (NCT02790437).
Imlifidase was administered up to 24 h before living or deceased donor kidney transplantation. DSAs were monitored before transplantation, at days 7 and 28, and at 5 y posttransplant.
At 5 y, 7 of 8 participants were alive. One of these 7 had suboptimal graft function secondary to donor-derived disease but remained dialysis independent. Three participants had antibody-mediated rejection (AMR), which occurred in the first 30 d in all cases and was successfully treated. No new episodes of suspected or biopsy-proven AMR occurred after 30 d posttransplant. Seven participants had DSA rebound. DSAs commonly persisted 5 y posttransplant, although they were generally lower strength compared with pre-imlifidase. Dilution studies of sensitized serum enabled the identification of lower AMR risk phenotypes for persisting DSAs. Severe and/or opportunistic infections were not observed at greater than expected frequency.
Five-year outcomes of imlifidase-enabled incompatible transplants are overall favorable. DSA rebound is common, but antibody strength lessens in the long term, and longitudinally persisting DSAs did not lead to premature graft failure.
伊姆利菲酶是一种可切割IgG的内肽酶，在欧洲有条件获批用于高度致敏患者肾移植前的脱敏治疗。我们报告了来自单一中心的临床试验参与者接受伊姆利菲酶进行不相容移植前脱敏治疗（NCT02790437）的5年结局和供体特异性抗体（DSA）水平。
在活体或 deceased 供体肾移植前至多24小时给予伊姆利菲酶。在移植前、第7天和第28天以及移植后5年监测DSA。
5年后，8名参与者中有7名存活。这7名参与者中的1名因供体源性疾病导致移植肾功能欠佳，但仍无需透析。3名参与者发生了抗体介导的排斥反应（AMR），所有病例均发生在移植后的前30天内，且均成功治疗。移植后30天之后未发生新的疑似或经活检证实的AMR发作。7名参与者出现了DSA反弹。DSA通常在移植后5年持续存在，尽管与使用伊姆利菲酶前相比强度普遍较低。对致敏血清的稀释研究有助于识别持续存在DSA的较低AMR风险表型。未观察到严重和/或机会性感染的发生频率高于预期。
伊姆利菲酶促成的不相容移植的5年结局总体良好。DSA反弹很常见，但抗体强度长期降低，且长期持续存在的DSA并未导致移植肾过早失功。
