Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Nephrol Dial Transplant. 2019 Jun 1;34(6):1056-1063. doi: 10.1093/ndt/gfy316.
Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs.
To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay.
Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P = 0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P = 0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11).
This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.
移植前供体特异性抗人类白细胞抗原(HLA)抗体(DSA)与移植肾存活率降低有关,而非供体特异性抗 HLA 抗体(nDSA)的临床相关性更具争议性。本研究旨在比较 DSA 和 nDSA 的临床相关性。
为消除供体和时代相关因素,作为一项评估 1995 年至 2005 年间所有移植的荷兰多中心研究的事后配对肾移植分析的一部分,对可获得移植前血清样本的患者进行了分析。采用 Luminex 单抗原珠法检测 HLA 抗体。
在 3237 例死亡供体移植中,我们确定了 115 对受体接受同一供体的肾脏移植,其中一名受体为 DSA 阳性,另一名受体无抗 HLA 抗体。移植前存在 DSA 的患者 10 年死亡风险的移植物存活率显著降低(55%比 82%,P=0.0001)。我们发现 192 对受体中,其中一名受体为 nDSA 阳性(针对 I 类和/或 II 类),另一名受体无抗 HLA 抗体。对于存在针对 I 类或 II 类的 nDSA 的患者,与无抗 HLA 抗体的患者相比,移植物存活率没有显著差异(74%比 77%,P=0.79)。只有在同时存在针对 I 类和 II 类 nDSA 的患者中,移植物存活率才有下降趋势(58%,P=0.06)。最后,在一小部分 42 对受体中,DSA 阳性受体的 10 年移植物存活率为 49%,而 nDSA 阳性受体的 10 年移植物存活率为 68%(P=0.11)。
本配对肾移植分析证实,在死亡供体移植中,移植前 DSA 的存在是移植物丢失的风险标志物,而非供体特异性抗体(nDSA)通常与移植物存活率降低无关。亚组分析表明,只有在广泛致敏的患者中,同时存在针对 I 类和 II 类的 nDSA 时,nDSA 可能是长期移植物丢失的风险标志物。