Kroshus T J, Dalmasso A P, Leventhal J R, John R, Matas A J, Bolman R M
Department of Surgery, University of Minnesota, Minneapolis, USA.
J Surg Res. 1995 Jul;59(1):43-50. doi: 10.1006/jsre.1995.1130.
Hyperacute rejection of a pig-to-primate organ xenograft is triggered by binding of anti-pig endothelial cell antibodies to the vascular endothelium of the xenograft and complement activation. Xenograft survival can be prolonged by pretransplant depletion of antibody with plasmapheresis or organ perfusion. However, these techniques have disadvantages for use immediately pretransplant or in the post-transplant period, including a marked reduction in coagulation proteins. To remove IgM and IgG from human plasma we employed a reusable Ig-binding column containing polyclonal anti-human IgG (heavy chain- and light chain-specific) conjugated to Sepharose beads (Therasorb, Baxter Corp.). Human blood was separated into plasma and cell fractions. Column absorption of plasma followed by recombination of plasma and cell fractions in the perfusion system resulted in 90.5 and 86.0% reduction in total IgG and IgM, respectively, and in a 47.0 and 69.4% reduction in IgG and IgM anti-pig endothelial cell antibodies, respectively. When the cellular fraction was recombined with untreated plasma and used to perfuse pig hearts in an ex vivo perfusion system, there was rapid cessation of normal cardiac rhythm (25.2 +/- 5.6 min) and intense deposition of Igs, complement proteins, and fibrin in the tissues. In contrast, perfusion with blood containing column-absorbed plasma was able to sustain cardiac function, with normal sinus rhythm maintained for 258 +/- 48.1 min, without tissue deposition of IgM or complement proteins and minimal deposition of IgG. We conclude that column absorption can be used effectively to deplete plasma of anti-pig endothelial cell antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
猪到灵长类动物的器官异种移植超急性排斥反应是由抗猪内皮细胞抗体与异种移植血管内皮结合并激活补体所引发的。通过血浆置换或器官灌注在移植前清除抗体可延长异种移植的存活时间。然而，这些技术在移植前即刻或移植后使用存在缺点，包括凝血蛋白显著减少。为了从人血浆中去除IgM和IgG，我们使用了一种可重复使用的Ig结合柱，其含有与琼脂糖珠偶联的多克隆抗人IgG（重链和轻链特异性）（Therasorb，百特公司）。将人血分离成血浆和细胞部分。血浆经柱吸收后，在灌注系统中将血浆和细胞部分重新组合，结果总IgG和IgM分别减少了90.5%和86.0%，抗猪内皮细胞抗体的IgG和IgM分别减少了47.0%和69.4%。当细胞部分与未处理的血浆重新组合并用于在体外灌注系统中灌注猪心脏时，正常心律迅速停止（25.2±5.6分钟），并且组织中Ig、补体蛋白和纤维蛋白大量沉积。相比之下，用含有经柱吸收血浆的血液进行灌注能够维持心脏功能，正常窦性心律维持258±48.1分钟，没有IgM或补体蛋白的组织沉积，IgG沉积极少。我们得出结论，柱吸收可有效地用于清除血浆中的抗猪内皮细胞抗体。（摘要截短于250字）
