The Role of Protein Glycosylation in Allergy

Abstract

The asparagine-linked carbohydrate moieties of plant and insect glycoproteins are the most abundant environmental immune determinants. They are the structural basis of what is known as cross-reactive carbohydrate determinants (CCDs). Despite some structural variation, the two main motifs are the xylose and the core-3-linked fucose, which form the essential part of two independent epitopes. Plants contain both epitopes, insect glycoproteins only fucose. These epitopes and other fucosylated determinants are also found in helminth parasites where they exert remarkable immunomodulatory effects. About 20% or more of allergic patients generate specific anti-glycan IgE, which is often accompanied by IgG. Even though antibody-binding glycoproteins are widespread in pollens, foods and insect venoms, CCDs do not appear to cause clinical symptoms in most, if not all patients. When IgE binding is solely due to CCDs, a glycoprotein allergen thus can be rated as clinical irrelevant allergen. Low binding affinity between IgE and plant N-glycans now drops out as a plausible explanation for the benign nature of CCDs. This rather may result from blocking antibodies induced by an incidental ‘immune therapy’ (‘glyco-specific immune therapy’) exerted by everyday contact with plant materials, e.g. fruits or vegetables. The need to detect and suppress anti-CCD IgE without interference from peptide epitopes can be best met by artificial glycoprotein allergens. Hydroxyproline-linked arabinose (single β-arabinofuranosyl residues) has been identified as a new IgE-binding carbohydrate epitope in the major mugwort allergen. However, currently the occurrence of this O-glycan determinant appears to be rather restricted.

Allergenicity Assessment of a Genetically Modified Protein-Recombinant Human Lactoferrin

“…The differences between rhLF and hLF in N-glycosylation profiles were consistent with the widely held view that glycosylation is species-and tissue/cell-specific [34]. Importantly, neither glycan structures (fucose and xylose substitutions at specific sites) that are known to be responsible for irrelevant IgE binding in some subjects [35] nor alpha-galactose that has been demonstrated to cause adverse immunological reactions [36] was detected on rhLF [37].…”

The red meat allergy syndrome in Sweden

“…Not only proteins but also carbohydrates can stimulate the production of IgE antibodies and be strong inducers of 2 responses [33]. e current estimate is that 15-30 % of allergic patients generate speci c anti-carbohydrate IgE antibodies [34], but this IgE response has very little clinical relevance [35].…”

A proteomic study of the major allergens from yellow jacket venoms

“…The structures of the Asn-linked oligosaccharides of Hyases from V. vulgaris have recently been determined and shown to be cross-reactive carbohydrate determinants (CCDs) due to the core a1,3-linked fucose [12,13]. CCDs are a frequent cause of cross-reactions of patients' sera with allergens from insects and other sources [3,14,15] but appear to be of low clinical significance [13,16,17].…”