Knosalla C, Gollackner B, Dor F J M F, Cooper D K C
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Building 149-9019, 13th Street, Boston, MA 02129, USA.
Curr Drug Targets Cardiovasc Haematol Disord. 2002 Dec;2(2):105-19. doi: 10.2174/1568006023337574.
Xenotransplantation, involving the transplantation of pig organs into humans, would resolve the current shortage of organs. It involves, however, a new therapeutic approach to organ transplantation. The presence of natural antibody in primates directed against Galalpha1,3Gal epitopes on pig vascular endothelium leads to early antibody-mediated rejection. An elicited antibody response against the same target epitopes as well as against nonGal antigens intensifies the immune destruction of the organ. Even the minimal deposition of antibody appears to lead to the development of a consumptive coagulopathy that can be fatal. Approaches being investigated to overcome these barriers include depletion and inhibition of natural antibody and complement, and suppression of the elicited T cell-dependent antibody and cellular responses. In addition, however, physiologic incompatibilities between human and pig, particularly those relating to coagulation, may enhance or complicate the immune process, and may require additional therapeutic measures. Current approaches aimed at achieving successful xenotransplantation also include investigation of agents that prevent potential xenozoonotic infection of the recipient. At present, therefore, the therapeutic interventions required to attempt to overcome the barriers to xenotransplantation are multiple. Work indicating progress in the breeding of pigs that do not express the critical Galalpha1,3Gal epitopes, however, is encouraging. The introduction of these pigs may greatly reduce the therapy required, and may ultimately allow the development of methods to induce tolerance to the transplanted pig organ.
异种移植，即将猪器官移植到人体中，有望解决当前器官短缺的问题。然而，这涉及到一种全新的器官移植治疗方法。灵长类动物体内存在针对猪血管内皮细胞上Galα1,3Gal表位的天然抗体，这会引发早期抗体介导的排斥反应。针对相同靶表位以及非Gal抗原引发的抗体反应，会加剧对器官的免疫破坏。即使是极少量的抗体沉积，似乎也会引发消耗性凝血病，这可能是致命的。目前正在研究的克服这些障碍的方法包括清除和抑制天然抗体及补体，以及抑制引发的T细胞依赖性抗体和细胞反应。然而，除此之外，人与猪之间的生理不相容性，尤其是与凝血相关的不相容性，可能会加剧免疫过程或使其变得更加复杂，这可能需要额外的治疗措施。目前旨在实现成功异种移植的方法还包括研究能够预防受体潜在异种动物感染的药物。因此，目前试图克服异种移植障碍所需的治疗干预措施是多方面的。不过，有研究表明，在培育不表达关键Galα1,3Gal表位的猪方面取得了进展，这令人鼓舞。引入这些猪可能会大大减少所需的治疗，并最终可能催生出诱导对移植猪器官产生耐受性的方法。
