King's College London, MRC Centre for Transplantation, London, UK.
Welcome Trust Sanger Institute, Human Genetics, Cambridge, UK.
Am J Transplant. 2018 Jun;18(6):1370-1379. doi: 10.1111/ajt.14594. Epub 2018 Feb 1.
Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.
免疫抑制的改善改变了已故供体同种异体移植物的短期存活率，但没有改变其长期失败的速率。供体和受者 HLA 之间的不匹配在急性和慢性同种异体免疫反应中对移植物起着重要作用。在临床相关 HLA 位点的完美匹配并不能免除免疫抑制的需要，这表明额外的遗传变异在短期和长期移植物结果中都起着关键作用。通过结合来自英国和欧盟跨国队列的患者数据和样本，我们进行了首次全基因组关联研究，分析了 2094 对完整肾移植对供体和受者 DNA 的影响，并在 5866 对完整对中进行了复制。我们研究了根据优先 HLA 匹配分配的已故供体移植物，这为 HLA 遗传效应提供了一些控制。在 HLA 区域之外，没有发现与长期或短期同种异体移植物存活有关的强烈供体或受体遗传效应。我们讨论了对未来研究和临床应用的影响。
