Immune responses to the alpha-Gal xenoantigen

在许多相关器官完全不可逆转地衰竭的情况下，成功的治疗方法是用新的器官代替，即进行移植。众所周知，可供移植的器官远远少于所需的数量。这意味着对于那些支持性治疗可用的情况，例如：对于人工肾脏，患者必须通过这种方法来维持，然而对于其他器官，如心脏、肺和肝脏，还没有机械替代品。如果这些病人不接受移植，他们就会死亡。解决这个问题的办法是使用动物器官。这被称为异种移植。猪是最合适的供体，然而，尽管猪与人类有许多相似之处，使猪成为合适的供体，但在临床上使用猪异种移植之前，仍有许多差异需要克服。这些差异存在于非常细微的分子水平上，阻碍了猪器官与人类受体的正常整合。可以确定的是，导致这种排斥反应的最重要的区别是猪有而人类没有的像血型一样的糖分子。这被称为Gal，它也存在于大多数动物物种中，我们已经通过基因改造从一种老鼠身上完全去除了它。不幸的是，还不可能在猪身上进行这种改变。然而，转基因小鼠为我们提供了一个测试模型，以精确地确定Gal抗原在多大程度上以及通过何种机制负责排斥过程。

The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace the organ with a new one i.e. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there is no mechanical substitute. If these patients do not receive a transplant, they die. A solution to this problem is to use organs from animals. This is called xenotransplantation. The pig is the most suitable donor, however despite the many similarities to humans which make pigs suitable, there are many differences which are still to be overcome before we can use pig xenotransplants clinically. These differences are at a very fine molecular level and prevent the normal integration of the pig organ into the human recipient. It is well established that the single most important difference which causes this rejection is a sugar molecule like a blood group which pigs have but humans do not. This is called Gal. This is also present in most animal species and we have completely removed it from a strain of mice by genetic modification. Unfortunately it has not been possible to make this change in pigs. However, the genetically modified mice give us a test model to determine precisely how much and by what mechanisms the Gal antigen is responsible for the rejection process.