Potential impact of the non-human sialic acid N-glycolylneuraminic acid on transplant rejection risk.
Potential impact of the non-human sialic acid N-glycolylneuraminic acid on transplant rejection risk.
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DOI：
10.1111/j.1399-3089.2011.00622.x
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发表时间：
2011-01
影响因子：
3.9
通讯作者：
Varki A
中科院分区：
文献类型：
--
作者：
Padler-Karavani V;Varki A
异种移植临床应用的一个主要障碍是免疫原性异种抗原的表达，这些异种抗原为异种移植物提供免疫识别靶点，导致宿主免疫激活，从而导致排斥反应或植入性差。其中最著名的异种抗原是由Galili及其同事表征的“αGal”表位(GalGalα1−3Galβ1−(3)4GlcNAc-R，其中R是潜在的糖结合物)。除东半球灵长类动物外，大多数哺乳动物都广泛表达该表位，并被大量循环中的人类抗α-Gal抗体识别。这种抗体在人类出生后普遍通过暴露于具有相似表位的肠道细菌而被诱导(2)，因此异种移植的困难甚至鼓励生产α1，3-半乳糖基转移酶基因敲除的猪(4)作为一种潜在的解决方案。但是，第二类抗碳水化合物异种抗体识别携带非人类唾液酸N-羟基神经氨酸(Neu5Gc)(5-9)的糖链。与αGal的情况不同，Neu5Gc-葡聚糖作为异种抗原的潜在影响没有得到很好的认识。在这里，我们讨论了这两种异种抗原的异同(摘要和比较参见表1)，结论是抗Neu5Gc抗体不仅与异种移植有关，而且与异体移植甚至自体移植有关，如果采用需要使用动物材料的体外培养阶段的方法，包括基于干细胞的治疗。
A major obstacle to clinical applications of xenotransplantation is the expression of immunogenic xenoantigens that provide targets for immune recognition of xenografts, leading to activation of host immunity and consequent rejection or poor engraftment. Among the best known xenoantigens is the “αGal” epitope (Galα1− 3Galβ1−(3) 4GlcNAc-R, where R is an underlying glycoconjugate) characterized by Galili and colleagues. This epitope is widely expressed by most mammals other than old world primates and recognized by abundant circulating human anti-α-Gal antibodies (1). Such antibodies are universally induced after birth in humans via exposure to gut bacteria bearing similar epitopes (2), and the resulting difficulties in xenotransplantation (3) have even encouraged production of alpha1, 3-galactosyltransferase gene-knockout pigs (4) as a potential solution.However, a second class of anti-carbohydrate xenoantibody recognize glycans carrying the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc)(5–9). Unlike the case with αGal, the potential impact of Neu5Gc-glycans as xenoantigens is less well recognized. Here we address the similarities and differences between these two xenoantigens (see Table 1 for a summary and comparison), concluding that anti-Neu5Gc antibodies are of potential relevance not only to xenotransplantation, but also to allotransplantation and even to autotransplantation if methods are incorporated that require an ex-vivo culturing phase using animal materials, including stem-cell based therapies.
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影响因子：
3.7
作者：
Hayashi Y;Chan T;Warashina M;Fukuda M;Ariizumi T;Okabayashi K;Takayama N;Otsu M;Eto K;Furue MK;Michiue T;Ohnuma K;Nakauchi H;Asashima M
通讯作者：
Asashima M
影响因子：
4.4
作者：
Nguyen, DH;Tangvoranuntakul, P;Varki, A
通讯作者：
Varki, A
影响因子：
4.1
作者：
Hashii, Noritaka;Kawasaki, Nana;Yamaguchi, Teruhide
通讯作者：
Yamaguchi, Teruhide
影响因子：
4.1
作者：
Komoda, Hiroshi;Okura, Hanayuki;Matsuyama, Akifumi
通讯作者：
Matsuyama, Akifumi
影响因子：
3.9
作者：
Diswall, Mette;Angstrom, Jonas;Breimer, Michael E.
通讯作者：
Breimer, Michael E.