Hypersialylated type-I lactosamine-containing N-glycans found in Artiodactyla sera are potential xenoantigens
Hypersialylated type-I lactosamine-containing N-glycans found in Artiodactyla sera are potential xenoantigens
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偶蹄类血清中发现的高度唾液酸化的 I 型乳糖胺 N 聚糖是潜在的异种抗原
DOI：
10.1093/glycob/cws069
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发表时间：
2012
期刊：
影响因子：
4.3
通讯作者：
Hirabayashi J
中科院分区：
文献类型：
--
作者：
Sumiyoshi W;Nakakita S;Miyanishi N;Yamada K;Hasehira K;Nakakita Y;Hirabayashi J
人们对生物制剂，即人类起源的生物制药越来越感兴趣。迄今为止开发的大多数蛋白质药物，如免疫球蛋白和促红细胞生成素，都是分泌型糖蛋白;因此，必须去除任何来自动物细胞和血清的非人型聚糖，如αGal和NeuGc，以避免不良免疫原性反应。在这项研究中，我们在一组哺乳动物血清中广泛寻找潜在的异种抗原聚糖。结果，发现属于偶蹄目的血清（即牛、羔羊和山羊血清）含有大量高唾液酸化双触角聚糖，这些聚糖与含有独特四糖Siaα2-3Galβ1-3（Siaα2-6）GlcNAc的I型乳糖胺结构密切相关。在所有三种偶蹄目动物血清中，最丰富的结构是Siaα2-3Galβ1-3（Siaα2-6）GlcNAcβ1- 2 Man α1-3[Siaα2- 6 Gal β1-4GlcNAcβ1- 2 Man α1-6]Manβ1-4GlcNAcβ1-4GlcNAc。在牛血清中也存在大量（10%）的双重高唾液酸化双触角结构Siaα2-3Galβ1-3（Siaα2-6）GlcNAcβ1- 2 Man α1- 3 [Siaα2-3Galβ1-3（Siaα2-6）GlcNAc β1- 2 Man α1-6]Manβ1 - 4GlcNAcβ1-4GlcNAc。在牛、羔羊和山羊血清中，高唾液酸化聚糖占总唾液酸化聚糖的量分别为46%、26%和23%。另一方面，在包括人在内的其他动物的血清中不能检测到这种结构。这些动物中高唾液酸化聚糖的生物学功能和免疫原性仍有待阐明;然而，值得注意的是，由偶蹄目动物细胞和被牛血清污染的细胞生物合成的糖蛋白可能会增强人类患者中的不良抗原性。
There is increasing interest in biologics, i.e. human-originated biological pharmaceutics. Most of the protein drugs developed so far, such as immunoglobulins and erythropoietin, are secreted glycoproteins; as a result, any non-human-type glycans, such as αGal and NeuGc, derived from animal cells and sera must be removed to circumvent undesirable immunogenic reactions. In this study, we made an extensive search for potential xenoantigenic glycans among a panel of mammalian sera. As a result, sera belonging to the order Artiodactyla, i.e. bovine, lamb and goat sera, were found to contain substantial amounts of hypersialylated biantennary glycans closely associated with a type-I lactosamine structure containing a unique tetrasaccharide, Siaα2-3Galβ1-3(Siaα2-6)GlcNAc. In all three Artiodactyla sera, the most abundant structure was Siaα2-3Galβ1-3(Siaα2-6)GlcNAcβ1-2Manα1-3[Siaα2-6Galβ1-4GlcNAcβ1-2Manα1-6]Manβ1-4GlcNAcβ1-4GlcNAc. A dually hypersialylated biantennary structure, Siaα2-3Galβ1-3(Siaα2-6)GlcNAcβ1-2Manα1-3[Siaα2-3Galβ1-3(Siaα2-6)GlcNAcβ1-2Manα1-6]Manβ1-4GlcNAcβ1-4GlcNAc, was also abundant (10%) in bovine serum. The amount of hypersialylated glycans among total sialylated glycans was 46, 26 and 23% in bovine, lamb and goat sera, respectively. On the other hand, such structures could not be detected in the sera of other animals including human. The biological functions and the immunogenicity of the hypersialylated glycans in these animals remain to be elucidated; however, it is worth noting that glycoproteins biosynthesized from Artiodactyla cells and those contaminated with bovine serum might enhance undesirable antigenicity in human patients.