Hypersialylated type-I lactosamine-containing N-glycans found in Artiodactyla sera are potential xenoantigens

Abstract

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.

Preparation of asparagine-linked monoglucosylated high-mannose-type oligosaccharide from egg yolk

“…Instead, preparation of G1M9-glycan from natural source has been achieved by hydrazinolysis/acetylation of glycopeptides, followed by labeling of the reducing end by fluorescent tags. 14,15 In this report, we describe the preparation of Asn-linked monoglucosylated high-mannose-type oligosaccharide ( Fig. 1) from egg yolk IgY.…”

N-glycan profiling of bovine follicular fluid at key dominant follicle developmental stages

“…Hypersialylation has only recently been described in the bovine (Sumiyoshi et al 2012) and mouse serum (Hua et al 2013). However, similar linkages have previously been described in free oligosaccharides from bovine colostrums (Nemansky & Van den Eijnden 1992), human milk (Sumiyoshi et al 2004) and mucin-type O-linked glycans from human mucosal tissues (Brockhausen 2006).…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2011–2012

“…Unusually, the fucose was located on an Hypersialylated biantennary glycans in these species only. (Sumiyoshi, et al, 2012) Caenorhabditis elegans…”