Lefaucheur C, Suberbielle-Boissel C, Hill G S, Nochy D, Andrade J, Antoine C, Gautreau C, Charron D, Glotz D
Department of Nephrology and Renal Transplant, Hôpital Saint-Louis 1 Av Claude Vellefaux, FR-75010 Paris, France.
Contrib Nephrol. 2009;162:1-12. doi: 10.1159/000170788. Epub 2008 Oct 31.
Since the pioneering work of Patel and Terazaki, the presence of an anti-donor anti-body of the IgG isotype, as demonstrated by a lymphocytotoxic assay on T cells, has been a contraindication to transplantation, due to the very high rate of graft loss reported (>80% in the first few weeks posttransplant). The advent of more sensible and specific techniques of detection of anti-HLA antibodies (such as ELISA or Luminex techniques) has questioned this dogma, with a number of reports showing that transplantation, despite the presence of an donor-specific antibody (DSA), could be done without excessive graft losses, despite higher rates of rejection. We thus decided to retrospectively screen a cohort of 237 patients consecutively transplanted in our unit. This study analyzes the influence of preformed DSA, identified by HLA-specific ELISA assays, on graft survival and evaluates the incidence of antibody-mediated rejection (AMR). Kidney graft survival at 8 years was significantly worse in patients with DSA. The incidence of AMR in patients with DSA was 9-fold higher than in patients without DSA and led to a significantly worse graft survival. The prevalence for AMR in patients with DSA detected on historic serum was 32.3% and was significantly more elevated in patients with strongly positive DSA (score 6-8) and in patients with his-toric positive crossmatches. Interestingly, those patients with DSA that did not experience AMR had the same graft survival as patients without DSA. Thus, the presence of preformed DSA is strongly associated with increased graft loss in kidney transplants, related to an increased risk of AMR. Our findings demonstrate the importance of detection and charac-terization of DSA before transplantation. Stratification of this immunological risk should be used both to determine kidney allocation and to devise specific strategies for these patients.
自帕特尔（Patel）和寺崎（Terazaki）的开创性工作以来，通过T细胞淋巴细胞毒性试验证明存在IgG同种型的抗供体抗体，一直是移植的禁忌证，因为报告的移植物丢失率非常高（移植后最初几周内>80%）。更灵敏和特异的抗HLA抗体检测技术（如ELISA或Luminex技术）的出现对这一教条提出了质疑，许多报告表明，尽管存在供体特异性抗体（DSA），移植仍可进行，且不会出现过多的移植物丢失，尽管排斥率较高。因此，我们决定对在我们单位连续接受移植的237例患者进行回顾性筛查。本研究分析了通过HLA特异性ELISA检测确定的预先存在的DSA对移植物存活的影响，并评估了抗体介导的排斥反应（AMR）的发生率。有DSA的患者8年肾移植存活率明显较差。有DSA的患者中AMR的发生率比无DSA的患者高9倍，且导致移植物存活明显更差。在历史血清中检测到有DSA的患者中AMR的患病率为32.3%，在DSA强阳性（评分6-8）的患者和历史交叉配型阳性的患者中明显更高。有趣的是，那些未发生AMR的有DSA的患者与无DSA的患者移植物存活率相同。因此，预先存在的DSA与肾移植中移植物丢失增加密切相关，这与AMR风险增加有关。我们的研究结果证明了移植前检测和鉴定DSA的重要性。这种免疫风险分层应用于确定肾脏分配并为这些患者制定具体策略。
