Recent investigations into pig antigen and anti-pig antibody expression.
Recent investigations into pig antigen and anti-pig antibody expression.
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DOI：
10.1016/j.ijsu.2015.07.724
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Breimer ME
中科院分区：
文献类型：
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作者：
Byrne GW;McGregor CGA;Breimer ME
供体猪的基因工程以消除显性异种抗原半乳糖α 1，3半乳糖（Gal）的表达，已经在异种移植排斥的免疫生物学方面产生了巨大变化。抗体介导的GGTA-1 α-半乳糖基转移酶（GTKO）缺陷器官的异种移植排斥反应目前针对非Gal猪蛋白和碳水化合物抗原的组合。GTKO组织的聚糖分析未发现新的新抗原，但检测到高水平的N-乙酰神经氨酸（Neu 5Gc）修饰的糖蛋白和糖脂。人类产生抗Neu 5Gc抗体，在非常有限的临床研究中，有时显示猪组织激发后诱导的抗Neu 5Gc抗体应答。抗Neu 5Gc抗体在异种移植中的致病性尚不清楚，然而，由于对模拟抗Gal免疫至关重要的非人移植模型不产生抗Neu 5Gc抗体。在非人灵长类动物中异种移植后诱导的抗体针对猪内皮细胞蛋白的阵列和由猪B4 GALNT 2基因产生的聚糖。我们预期免疫抑制将显著影响诱导抗体应答的T细胞依赖性和非依赖性特异性，并且供体猪缺乏多种异种聚糖的合成对未来的研究将是重要的。
Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the immunobiology of xenograft rejection. Antibody mediated xenograft rejection of GGTA-1 α-galactosyltransferase (GTKO) deficient organs is now directed to a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis of GTKO tissues identified no new neo-antigens but detected high levels of N-acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show an induced anti-Neu5Gc antibody response after challenge with pig tissue. The pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however as non-human transplant models, critical for modelling anti-Gal immunity, do not produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non-human primates is directed to an array of pig endothelial cells proteins and to a glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression will significantly affect the T-cell dependent and independent specificity of an induced antibody response and that donor pigs deficient in synthesis of multiple xenogeneic glycans will be important to future studies.