Red meat allergic patients have a selective IgE response to the α-Gal glycan

Abstract

Galactose-α-1,3-galactose (α-Gal) is a mammalian carbohydrate with significance in a novel type of food allergy. Patients with IgE against α-Gal report severe allergic symptoms 3-6 h after consumption of red meat. We investigated whether IgE from red meat allergic patients recognizes other mammalian glycans than α-Gal or glycans from the plant kingdom and insects of importance in allergy. We found that none of the 24 red meat allergic patients investigated had an IgE antibody response against the other abundant mammalian glycan N-glycolylneuraminic acid or against cross-reactive carbohydrate determinants from plant or venom sources (nCup a 1, nArt v 1, and MUXF3). Deglycosylation of an α-Gal-containing protein, bovine thyroglobulin, significantly reduced the IgE response. In conclusion, we show that red meat allergic patients have a selective IgE response to the α-Gal glycan found in red meat. Other common glycans reactive in allergic disease are not targets of red meat allergic patients' IgE.

The quantity and quality of α-gal-specific antibodies differ in individuals with and without delayed red meat allergy

“…IgE recognition of BGG was completely abolished by α‐gal conjugated to BSA (Fig. 2) confirming that patients with delayed meat allergy selectively recognize α‐gal independently from the carrier protein 24.…”

“…Although IgE‐mediated, the symptoms occur atypically late for immediate hypersensitivity, namely 3–7 h after ingestion of red meat 23. The major allergen is not a protein but a mammalian oligosaccharide and removal of α‐gal dramatically reduces IgE binding to beef proteins 24. Several studies provided evidence that sensitization to α‐gal results from tick bites 11, 12, 25, 26.…”

“…Consequently, delayed meat allergy is not a consequence of oral but cutaneous sensitization to the α‐gal epitope expressed on proteins present in the gastrointestinal tract of these arthropods 27. Thereafter, individuals may develop allergic reactions due to IgE reactivity with α‐gal on mammalian proteins, for example murine and feline Ig 16, 24, 28. This pathophysiology is reminiscent of other, so‐called secondary food allergies, for example birch pollen‐related food allergy.…”

Peptidomics of an in vitro digested α-Gal carrying protein revealed IgE-reactive peptides

“…As galactose-β1,4-N-acetylglucosamine is a part of the complex BTG glycan, we used direct ELISA to conclude that red meat-allergic patients’ IgE did not bind galactose-β1,4-N-acetylglucosamine itself and that there was a slight difference in IgE binding to α-Gal di- and trisaccharides. We have previously shown that red meat allergic patients have a selective IgE response to the α-Gal glycan that does not involve the protein backbone and, that Neu5Gc is not the target of the IgE response 36 . Plum and colleagues have shown that the IgE binding is localized to both galactose molecules but the the galactose-α1,3-galactose-β1,4-N-acetylglucosamine was not included in their study 37 .…”

“…BTG was chosen as a model α-Gal-containing protein and deglycosylated thyroglobulin was obtained using enzymatic deglycosylation 36 . Pepsin activity was verified according to manufacturer’s instructions prior to experiments.…”