Accommodation using synthetic Gal Antigen in xenotransplantation

不和谐物种成员之间的移植，如猪对人的移植，会导致未修饰受体的超急性排斥反应。极快的排斥反应过程与受体异种反应性天然抗体抗半胱甘肽（1,3）半胱甘肽抗体和补体在供体器官内皮上的共沉积有关。在某些情况下，抗供体抗体从移植物受体的循环中暂时耗尽，也许还有其他操作，即使在抗体返回循环和补体系统恢复后，也可以延长血管化移植物的存活时间。这种情况被称为适应。虽然调节的机制尚不清楚，但如果调节可以实现，这是异种移植临床应用中一个重要的问题。我们尝试用猪甲状腺球蛋白亲和层析柱从人血清中吸收抗Gal抗体，然后从层析柱中洗脱有界抗体。在组织学检查中，猪胰岛可见人血清染色，但未见抗Gal抗体。因此，我们认为除了Gal抗原外，猪胰岛表面还存在一种可被抗Gal抗体识别的抗原。虽然不是一种去除抗体的方法，但在体内给药目标表位（Gal抗原）是阻断天然抗体与其靶点结合的有效方法。我们尝试用化学试剂或半乳糖苷酶两种方法合成半乳糖抗原。在ELISA实验中，合成的半乳糖抗原中和人血清抗半乳糖抗体能有效阻断与抗原的结合。由于合成Gal抗原的成本非常昂贵，我们不能尝试在体内使用。在临床异种移植中，利用合成抗原进行免疫吸附和以可溶性形式给药是预防超急性排斥反应的有效方法。

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.