Allen Katrina J, Mifsud Nicole A, Williamson Robert, Bertolino Patrick, Hardikar Winita
Gut and Liver Research Group, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
Liver Transpl. 2008 May;14(5):688-94. doi: 10.1002/lt.21443.
Liver cell transplantation in humans has been impeded by invariable loss of the graft. It is unclear whether graft loss is due to an immune response against donor hepatocytes. Transplantation with ABO-matched liver cells was performed in a patient with Crigler-Najjar type 1. After successful engraftment, there was a gradual loss of graft function. Solid-phase enzyme immunoassay testing and cell-complement cytotoxicity assays detecting preformed antibodies directed toward class I and/or class II human leukocyte antigen (HLA) molecules were negative. In contrast, a striking host alloresponse to either the HLA-B39 or C7 antigen was found, suggesting that a vigorous response to a defined mismatched HLA antigen contributed to graft loss in our patient. This study provides evidence that a T-cell-mediated immune mechanism could be responsible for human liver cell transplant graft loss. This finding warrants confirmation in future liver cell transplants in humans.
人类肝细胞移植一直因移植物的持续丢失而受阻。目前尚不清楚移植物丢失是否是由于针对供体肝细胞的免疫反应所致。对一名1型克里格勒 - 纳贾尔综合征患者进行了ABO血型匹配的肝细胞移植。成功植入后,移植物功能逐渐丧失。检测针对I类和/或II类人类白细胞抗原(HLA)分子的预先形成抗体的固相酶免疫测定试验和细胞补体细胞毒性试验均为阴性。相反,发现宿主对HLA - B39或C7抗原存在显著的同种异体反应,这表明对特定不匹配HLA抗原的强烈反应导致了我们患者的移植物丢失。这项研究提供了证据,表明T细胞介导的免疫机制可能是人类肝细胞移植移植物丢失的原因。这一发现有待在未来的人类肝细胞移植中得到证实。