Babu Adarsh, Andreou Avgi, Briggs David, Krishnan Nithya, Higgins Rob, Mitchell Dan, Barber Tom, Daga Sunil
Department of Nephrology and Transplantation, University Hospitals Coventry and Warwickshire, Coventry, UK.
Warwick Medical School, University of Warwick, Coventry, UK.
Clin Transpl. 2016;32:173-179.
Immunoglobulin G (IgG) antibodies against donor human leukocyte antigens (HLA) are monitored in the pre-and post-transplant period due to their established role in predicting rejection and renal allograft survival. However, the role of immunoglobulin M (IgM) anti-HLA donor-specific antibodies (DSA) is not fully understood, especially in highly-sensitized patients undergoing direct transplantation. We designed this study to determine whether IgM DSA predicts rejection episodes and/or graft failure. Samples from 92 patients who had undergone HLA-antibody incompatible transplants were tested at 5 time points: days -8 (pre-plasmapheresis), 0, 7, 14, and 30 using Luminex microbead assay with ethylenediaminetetraacetic acid containing wash buffer (LABScreen®, One Lambda, Canoga Park, CA). IgM was defined positive if the mean fluorescence values were greater than 2000. Presence of pre- and post-transplant IgM was correlated with early antibody mediated rejection episodes (within 30 days post-transplantation) and graft failure. Statistical analyses were performed using SPSS IBM software. Graft survival estimates were death-censored. The presence of pre-transplant IgM DSA did not predict rejection (p=0.83) or graft failure (p=0.424). The post-transplant IgM DSA levels peaked at day 14 (similar to IgG DSA levels). Presence of IgM DSA post-transplant (de novo and resynthesis) was not associated with rejection (p=0.83). However, post-transplant IgM was associated with graft failure (p=0.037). This study shows additional testing of post-transplant IgM DSA over and above IgG is important as post-transplant IgM DSA is associated with graft failure.
由于免疫球蛋白G(IgG)抗供体人类白细胞抗原(HLA)抗体在预测排斥反应和肾移植存活率方面已确立的作用,因此在移植前和移植后阶段对其进行监测。然而,免疫球蛋白M(IgM)抗HLA供体特异性抗体(DSA)的作用尚未完全明确,尤其是在接受直接移植的高敏患者中。我们设计了这项研究,以确定IgM DSA是否能预测排斥反应发作和/或移植失败。对92例接受HLA抗体不相容移植的患者的样本在5个时间点进行检测:-8天(血浆置换前)、0天、7天、14天和30天,使用含乙二胺四乙酸洗涤缓冲液的Luminex微珠检测法(LABScreen®,One Lambda,卡诺加公园,加利福尼亚州)。如果平均荧光值大于2000,则IgM定义为阳性。移植前和移植后IgM的存在与早期抗体介导的排斥反应发作(移植后30天内)和移植失败相关。使用SPSS IBM软件进行统计分析。移植存活率估计采用死亡截尾法。移植前IgM DSA的存在不能预测排斥反应(p=0.83)或移植失败(p=0.424)。移植后IgM DSA水平在第14天达到峰值(与IgG DSA水平相似)。移植后IgM DSA(新生和再合成)的存在与排斥反应无关(p=0.83)。然而,移植后IgM与移植失败相关(p=0.037)。这项研究表明,除了IgG之外,对移植后IgM DSA进行额外检测很重要,因为移植后IgM DSA与移植失败相关。