Immune responses to the alpha-Gal xenoantigen

对 α-Gal 异种抗原的免疫反应

• 批准号: nhmrc : 204700
• 负责人: Prof Anthony D'Apice
• 金额: $ 18.07万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/immune-responses-alpha-gal-xenoantigen/99689
• 关键词: Immune; responses; alpha; Gal; xenoantigen

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.

成功治疗许多相关器官完全和不可逆转地衰竭的疾病是用新的器官替换器官，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。人造肾脏，病人必须靠这种方法来维持，但对于其他器官，如心脏，肺和肝脏，没有机械替代品。如果这些患者不接受移植，他们就会死亡。解决这个问题的一个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，使猪适合，但在我们能够在临床上使用猪异种移植之前，仍有许多差异需要克服。这些差异处于非常精细的分子水平，并阻止猪器官正常整合到人类受体中。众所周知，导致这种排斥反应的最重要的一个差异是糖分子，就像猪有而人类没有的血型。它被称为Gal。这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小鼠中完全去除了它。不幸的是，在猪身上无法实现这种改变。然而，转基因小鼠为我们提供了一个测试模型，以精确确定Gal抗原在排斥过程中的作用程度和机制。