抗HLA II类抗体在交叉配型阳性的活体供肾移植中对脱敏治疗最具抗性：病例系列研究
Anti-HLA Class II Antibodies Are the Most Resistant to Desensitization in Crossmatch-positive Living-donor Kidney Transplantations: A Patient Series.
作者信息
de Weerd Annelies E, Roelen Dave L, Betjes Michiel G H, Clahsen-van Groningen Marian C, Haasnoot Geert W, Kho Marcia M L, Reinders Marlies E J, Roodnat Joke I, Severs David, Karahan Gonca E, van de Wetering Jacqueline
机构信息
Department of Internal Medicine, Erasmus MC Transplant Institute, University Medical Center, Rotterdam, The Netherlands.
Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
出版信息
Transplant Direct. 2024 Aug 29;10(9):e1695. doi: 10.1097/TXD.0000000000001695. eCollection 2024 Sep.
BACKGROUND
In HLA-incompatible kidney transplantation, the efficacy of desensitization in terms of anti-HLA antibody kinetics is not well characterized. We present an overview of the course of anti-HLA antibodies throughout plasma exchange (PE) desensitization in a series of crossmatch-positive patients.
METHODS
All consecutive candidates in the Dutch HLA-incompatible kidney transplantation program between November 2012 and January 2022 were included. The eligibility criteria were a positive crossmatch with a living kidney donor and no options for compatible transplantation. Desensitization consisted of 5-10 PE with low-dose IVIg.
RESULTS
A total of 16 patient-donor pairs were included. Patients had median virtual panel-reactive antibody of 99.58%. Cumulative donor-specific anti-HLA antibody (cumDSA) mean fluorescence intensity (MFI) was 31 399 median, and immunodominant DSA (iDSA) MFI was 18 677 for class I and 21 893 for class II. Median anti-HLA antibody MFI response to desensitization was worse in class II as compared with class I ( < 0.001), particularly for HLA-DQ. Class I cumDSA MFI decreased 68% after 4 PE versus 53% in class II. The decrease between the fifth and the 10th PE sessions was modest with 21% in class I versus 9% in class II. Antibody-mediated rejection occurred in 85% of patients, with the iDSA directed to the same mismatched HLA as before desensitization, except for 3 patients, of whom 2 had vigorous rebound of antibodies to repeated mismatches (RMMs). Rebound was highest (86%) in RMM-DSA with prior grafts removed (transplantectomy n = 7), lower (39%) in non-RMM-DSA (n = 30), and lowest (11%) for RMM-DSA with in situ grafts (n = 5; = 0.018 for RMM-DSA transplantectomy versus RMM-DSA graft in situ). With a median follow-up of 59 mo, 1 patient had died resulting in a death-censored graft survival of 73%.
CONCLUSIONS
Patients with class II DSA, and particularly those directed against HLA-DQ locus, were difficult to desensitize.
背景
在HLA不相合肾移植中，脱敏治疗在抗HLA抗体动力学方面的疗效尚未得到充分表征。我们概述了一系列交叉配型阳性患者在血浆置换（PE）脱敏治疗过程中抗HLA抗体的变化情况。
方法
纳入2012年11月至2022年1月荷兰HLA不相合肾移植项目中的所有连续候选者。入选标准为与活体肾供者交叉配型阳性且无合适的相容性移植供者。脱敏治疗包括5 - 10次PE联合小剂量静脉注射免疫球蛋白（IVIg）。
结果
共纳入16对患者 - 供者配对。患者虚拟群体反应性抗体（vPRA）中位数为99.58%。累积供者特异性抗HLA抗体（cumDSA）平均荧光强度（MFI）中位数为31399，免疫显性DSA（iDSA）MFI在I类为18677，II类为21893。与I类相比，II类抗HLA抗体MFI对脱敏治疗的反应更差（<0.001），尤其是针对HLA - DQ。4次PE后，I类cumDSA MFI下降68%，而II类为53%。在第5次和第10次PE治疗之间，下降幅度较小，I类为21%，II类为9%。85%的患者发生了抗体介导的排斥反应，iDSA针对的HLA错配与脱敏治疗前相同，但有3例患者除外，其中2例对重复错配（RMM）的抗体出现强烈反弹。在已切除先前移植肾（移植肾切除术n = 7）的RMM - DSA中反弹率最高（86%），在非RMM - DSA（n = 30）中较低（39%），在原位移植肾的RMM - DSA中最低（11%）（RMM - DSA移植肾切除术与RMM - DSA原位移植肾相比，P = 0.018）。中位随访59个月，1例患者死亡，死亡校正后的移植肾存活率为73%。
结论
II类DSA患者，尤其是针对HLA - DQ位点的患者，难以脱敏。
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