Table_4_The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study.docx

BackgroundPre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).
MethodsWe investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.
ResultsPre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR.
ConclusionOur results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.

背景：移植前供者特异性抗体（donor specific antibodies, DSA），即靶向供者器官内存在的非己人类白细胞抗原（human leukocyte antigen, HLA）蛋白变体的抗体，已被证实与肾移植术后不良预后相关。然而，针对检测到的DSA的平均荧光强度（mean fluorescence intensity, MFI）以及其靶HLA抗原的影响，在具备完整虚拟交叉配型（virtual cross-match, vXM）的大型队列中尚未得到确定性研究。
方法：本研究纳入411例DSA阳性肾移植受者与1804例DSA阴性对照者，探究移植前DSA对抗体介导排斥反应（antibody-mediated rejection, ABMR）发生风险、移植物丢失以及估算肾小球滤过率（estimated glomerular filtration rate, eGFR）下降速率的影响。
结果：移植前DSA与ABMR发生风险、移植物丢失风险以及eGFR加速下降的风险显著升高相关。靶向I类与II类HLA抗原的DSA均与ABMR风险升高显著相关，但仅靶向II类HLA抗原的DSA与移植物丢失存在关联。DSA的MFI值对预后存在显著影响：II类HLA DSA在MFI处于500~1000区间时即与ABMR相关，而I类HLA DSA在相近的低MFI值下未对预后产生影响。此外，仅针对HLA-DP的DSA，在ABMR发生、eGFR加速下降以及移植物丢失方面的风险与针对HLA-DR的DSA相当。
结论：本研究结果对器官分配系统中所使用的vXM算法的构建与优化具有重要指导价值。本研究数据表明，应同时考量检测到的DSA的HLA抗原靶标与累积MFI值，且可针对I类与II类靶向DSA设置差异化的MFI临界值。