Cucchiari David, Mancebo-Sierra Esther, Caro José Luis, Meneghini Maria, Pérez-Saez María José, López Beatriz Romero, Redondo-Pachón Dolores, Arana Carolt, Bestard Oriol, Andrés Amado, Moreso Francesc, Crespo Marta, Palou Eduard, Diekmann Fritz
Department of Nephrology and Kidney Transplantation, Hospital Clínic, Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain; REDinREN (RD16/0009/0013), Instituto de Salud Carlos III, Madrid, Spain.
Immunology Department, University Hospital 12 de Octubre, Research Institute Hospital 12 Octubre (imas12), Madrid, Spain.
Kidney Int. 2025 Jun 6. doi: 10.1016/j.kint.2025.04.031.
In kidney transplant candidates with calculated Panel Reactive Antibody (cPRA)≥99.9%, looking for perfect HLA compatibility may delay transplantation beyond a reasonable waiting time. However, the presence of preformed donor-specific antibody (DSA) does not always lead to antibody-mediated rejection. Here, we present the results of a delisting strategy for kidney transplant candidates with cPRA≥99.9% employed in four Spanish transplant centers May 2022-August 2023.
Briefly, HLA antigens were delisted if their mean fluorescence intensity (MFI) in current and historical samples was lower than 5,000, with the goal to decrease cPRA to ≤99.0%. If this first step was unsuccessful, HLA antibodies with an MFI under 10,000, or any MFI for anti-HLA-DP and anti-HLA-DRB3/4/5 were considered for delisting. Additional criteria included their 1/16 dilutions response and complement-binding activity (C3d or C1q), ideally avoiding antibodies targeting a cross-reactive epitope groups/eplet pattern and repeated mismatches with previous donors.
In total, 48 patients underwent HLA-antigen delisting after a median 5.6 years on the waiting list, lowering their cPRA to 98.3%. Thirty (62.5%) patients received an acceptable donor offer 98[52-154] days after delisting, of which 18 (60.0%) had negative flow cytometry and complement-dependent cytotoxicity crossmatches and underwent direct transplantation without additional desensitization with the enzyme imlifidase. Among these, sixteen patients (83.3%) had at least one preformed DSA, with an immunodominant MFI of 7245[3857-18322]. In these patients, after one-year follow-up, antibody-mediated rejection occurred in seven cases (43.7%) and graft survival was 87.5%.
Our study shows that careful antigen delisting enhances access to transplantation for patients with cPRA ≥99.9%. While this approach carries a significant risk of acute rejection, it is associated with reasonable short-term graft survival.
在计算得出的群体反应性抗体（cPRA）≥99.9%的肾移植候选者中，寻找完美的人类白细胞抗原（HLA）相容性可能会使移植延迟到超出合理等待时间。然而，预先形成的供体特异性抗体（DSA）的存在并不总是导致抗体介导的排斥反应。在此，我们展示了2022年5月至2023年8月在四个西班牙移植中心采用的针对cPRA≥99.9%的肾移植候选者的除名策略的结果。
简而言之，如果当前和历史样本中HLA抗原的平均荧光强度（MFI）低于5000，则将其从名单中剔除，目标是将cPRA降至≤99.0%。如果第一步不成功，则考虑将MFI低于10000的HLA抗体，或抗HLA-DP和抗HLA-DRB3/4/5的任何MFI的抗体从名单中剔除。其他标准包括它们的1/16稀释反应和补体结合活性（C3d或C1q），理想情况下避免针对交叉反应表位组/表位模式的抗体以及与先前供体的重复错配。
总共有48名患者在等待名单上中位等待5.6年后接受了HLA抗原除名，将他们的cPRA降至98.3%。30名（62.5%）患者在除名后98[52 - 154]天收到了可接受的供体提议，其中18名（60.0%）患者流式细胞术和补体依赖细胞毒性交叉配型为阴性，并且在未使用酶艾姆利菲酶进行额外脱敏的情况下直接进行了移植。在这些患者中，16名（83.3%）患者至少有一个预先形成的DSA，其免疫显性MFI为7245[3857 - 18322]。在这些患者中，经过一年的随访，7例（43.7%）发生了抗体介导的排斥反应，移植肾存活率为87.5%。
我们的研究表明，仔细的抗原除名增加了cPRA≥99.9%患者的移植机会。虽然这种方法有急性排斥的重大风险，但它与合理的短期移植肾存活率相关。
