Accommodation using synthetic Gal Antigen in xenotransplantation

在不协调的物种之间进行移植，如猪与人之间的移植，会导致未经修饰的受体发生超急性排斥反应。极快的排斥反应过程与受体异种反应性天然抗体抗Galpha(1，3)Gal抗体和补体在供体器官内皮细胞上共沉积有关。在某些情况下，从移植受体的循环中暂时耗尽抗供体抗体，也许还有其他操作，即使在抗体返回循环和补体系统恢复之后，也可以延长血管化移植物的存活时间。这种情况被称为调节。尽管调节的机制尚不清楚，但能否实现调节是异种移植临床应用中的一个重要问题。我们尝试用猪甲状腺球蛋白亲和层析柱从人血清中吸附抗Gal抗体，然后从柱子中洗脱结合抗体。在组织学检查中，猪胰岛与人血清染色清晰，但未见抗Gal抗体。因此，我们得出结论，猪岛表面除Gal抗原外，还存在一种被抗Gal抗体识别的抗原，虽然不是一种去除抗体的方法，但体内注射靶表位(Gal抗原)是阻断天然抗体与其靶标结合的有效方法。我们尝试用化学试剂和α-半乳糖苷酶两种方法合成Gal抗原。人工合成的Gal抗原能有效中和人血清中的抗Gal抗体，并能有效地阻断与抗原的结合。由于Gal抗原的合成成本非常昂贵，我们不能尝试在体内使用。在临床异种移植中，使用联体抗原的免疫吸附和可溶性抗原管理有可能成为预防超急性排斥反应的有效治疗方法。

Transplantation between members of discordant species, such as pig to human, result in hyperacute rejection in unmodified recipient. The extremely rapid rejection process is associated with codeposition of recipient xenoreactive natural antibody named anti-Galalpha (1,3) Gal antibody and complement on the endothelium of the donor organ. In some cases the temporary depletion of antidonor antibody from the circulation of a graft recipient and perhaps other manipulations allows the prolonged survivl of a vascularized graft even after the antibody return to the circulation and the complement system is restored. This condition is called accommodation.Though the mechanism underlyning accommodation is not known, if accommodation can be achieved which is an issue of importance in the clinical application of xenotransplantation. We tried to absorb anti Gal antibody from human serum using the pig thyroglobulin affinity chromatography colum and then bounded antibodies were eluted from the colum. In the histological examination, pig islets were stained with human serum clearly, but not anti Gal antibody. Therefore, we concluded that there is an another antigen except Gal antigen which is recognized by anti Gal antibody on the surface of pig islets.While not a method to remove antibodies, adoministration of the target epitopes (Gal antigen) in vivo is an useful method to block the binding of natural antibody to their targets. We attempted to synthesis Gal antigen by two methods using chemical agents or alpha-galactosidase. Synthetic Gal antigen neutralized anti Gal antibody from human serum effectively resulted blocking to bind to antigen in ELISA assay. Since the cost of Gal antigen synthesis is very expensive we can not try to use in vivo. Immunoadsorption using syntetic antigen and antigen adoministration in solible form have an ability to come an effective therapy to prevent hyperacute rejection in clinical xenotransplantation.