Taniguchi S, Neethling F A, Korchagina E Y, Bovin N, Ye Y, Kobayashi T, Niekrasz M, Li S, Koren E, Oriol R, Cooper D K
Oklahoma Transplantation Institute, Baptist Medical Center, Oklahoma City, USA.
Transplantation. 1996 Nov 27;62(10):1379-84. doi: 10.1097/00007890-199611270-00001.
The major role of anti-alphaGal antibodies in the hyperacute rejection of pig organs by humans and baboons has been clearly demonstrated. Spacered alpha-galactose disaccharide (Gal(alpha1)-3Gal) hapten was produced by chemical synthesis and covalently attached to a flexible, hydrophilic polymer (PAA), which in turn was covalently coupled to macroporous glass beads, forming an immunoadsorbent that is mechanically and chemically stable and can be sterilized. The extracorporeal immunoadsorption (EIA) of anti-alphaGal antibodies using this column has been investigated in vivo in 3 baboons. In Baboon 1 (which had hyperacutely rejected a pig heart transplant 4 months previously, was not splenectomized, and did not receive any pharmacologic immunosuppression) the levels of anti-alphaGal antibody and antipig IgM and IgG, as well as serum cytotoxicity, fell significantly after each of 3 EIAs but were not eliminated. Serum cytotoxicity, antipig immunoglobulin and anti-alphaGal antibody rose steeply within 24 hr of the final EIA, suggesting that the return of cytotoxicity was associated with anti-alphaGa1 antibody. In Baboons 2 and 3 (which were immunologically naive and splenectomized, and received triple drug immunosuppressive therapy) serum cytotoxicity was totally eliminated and anti-alphaGal antibody and antipig IgM and IgG levels were greatly reduced by courses of EIA. In Baboon 2, cytotoxicity and all antibody levels remained negligible for approximately one week after the final (fourth) daily EIA. In Baboon 3, cytotoxicity and antibody levels were maintained low by intermittent EIA (over a period of 13 days) for almost 3 weeks, although antipig IgM began to rebound 4 days after the final EIA. We conclude that, in an immunosuppressed, splenectomized baboon, repeated EIA using a specific alphaGal disaccharide column will reduce antipig and anti-alphaGal antibody levels and serum cytotoxicity significantly for several days. This reduction in cytotoxicity will almost certainly be sufficient to delay the hyperacute rejection of a transplanted pig organ, but further studies are required to investigate whether it will be sufficient to allow accommodation to develop.
抗αGal抗体在人类和狒狒对猪器官超急性排斥反应中的主要作用已得到明确证实。间隔α-半乳糖二糖（Gal(α1)-3Gal）半抗原通过化学合成产生，并共价连接到柔性亲水性聚合物（PAA）上，该聚合物又与大孔玻璃珠共价偶联，形成一种机械和化学性质稳定且可消毒的免疫吸附剂。使用该柱对抗αGal抗体进行体外免疫吸附（EIA）已在3只狒狒体内进行了研究。在狒狒1（4个月前超急性排斥了猪心脏移植，未进行脾切除术，未接受任何药物免疫抑制）中，经过3次EIA后，抗αGal抗体、抗猪IgM和IgG水平以及血清细胞毒性均显著下降，但未消除。在最后一次EIA后24小时内，血清细胞毒性、抗猪免疫球蛋白和抗αGal抗体急剧上升，表明细胞毒性的恢复与抗αGal抗体有关。在狒狒2和3（免疫未接触过且进行了脾切除术，并接受三联药物免疫抑制治疗）中，通过EIA疗程，血清细胞毒性被完全消除，抗αGal抗体、抗猪IgM和IgG水平大幅降低。在狒狒2中，最后一次（第四次）每日EIA后约一周内，细胞毒性和所有抗体水平仍可忽略不计。在狒狒3中，通过间歇性EIA（持续两周），细胞毒性和抗体水平在近3周内保持较低，尽管在最后一次EIA后4天抗猪IgM开始反弹。我们得出结论，在免疫抑制、脾切除的狒狒中，使用特定αGal二糖柱进行重复EIA将在数天内显著降低抗猪和抗αGal抗体水平以及血清细胞毒性。这种细胞毒性的降低几乎肯定足以延迟移植猪器官的超急性排斥反应，但需要进一步研究以调查其是否足以促进适应性的形成。
