The α-Gal epitope - the cause of a global allergic disease

Abstract

The galactose-α-1,3-galactose (α-Gal) epitope is the cause of a global allergic disease, the α-Gal syndrome (AGS). It is a severe form of allergy to food and products of mammalian origin where IgE against the mammalian carbohydrate, α-Gal, is the cause of the allergic reactions. Allergic reactions triggered by parenterally administered α-Gal sources appear immediately, but those triggered via the oral route appear with a latency of several hours. The α-Gal epitope is highly immunogenic to humans, apes and old-world monkeys, all of which produce anti-α-Gal antibodies of the IgM, IgA and IgG subclasses. Strong evidence suggests that in susceptible individuals, class switch to IgE occurs after several tick bites. In this review, we discuss the strong immunogenic role of the α-Gal epitope and its structural resemblance to the blood type B antigen. We emphasize the broad abundance of α-Gal in different foods and pharmaceuticals and the allergenicity of various α-Gal containing molecules. We give an overview of the association of tick bites with the development of AGS and describe innate and adaptive immune response to tick saliva that possibly leads to sensitization to α-Gal. We further discuss a currently favored hypothesis explaining the mechanisms of the delayed effector phase of the allergic reaction to α-Gal. We highlight AGS from a clinical point of view. We review the different clinical manifestations of the disease and the prevalence of sensitization to α-Gal and AGS. The usefulness of various diagnostic tests is discussed. Finally, we provide different aspects of the management of AGS. With climate change and global warming, the tick density is increasing, and their geographic range is expanding. Thus, more people will be affected by AGS which requires more knowledge of the disease.

The human and mouse dendritic cell receptor DCIR binds to LRP1 N-glycans containing terminal galactoses, including the α-Gal antigen

“…35 Of note, tandem mass spectrometry (MS/MS) and antibody staining showed that mouse LRP1 N-glycans exhibit the terminal Galα1-3Galβ1-4GlcNAc (α-Gal) epitope (Figures 4B and S6), a unique carbohydrate antigen abundantly expressed on glycoconjugates of most mammals yet absent in humans. 36, 37 To determine which of these N-glycan structures are ligand(s) for hDCIR and mDCIR1, we performed an enzyme-linked lectin assay using neo-glycoproteins generated by covalent coupling of biantennary complex-type N-glycans with either terminal GlcNAc, Gal, α-Gal or α2,6-linked sialic residues to bovine serum albumin (BSA). We found that both hDCIR-ECD and mDCIR1-ECD strongly interact with biantennary complex-type N-glycans with terminal galactose residues, including those carrying the α-Gal epitope, but poorly or not at all with agalactosylated or sialylated N-glycans (Figure 4C).…”

“…alphagal syndrome, and hypersensitivity reactions to cetuximab, a chimeric mouse-human monoclonal antibody used to treat cancers of the bowel and neck. 36,37,[65][66][67] To our knowledge, hDCIR is the first human lectin described as interacting with the a-Gal epitope carried on glycoproteins, suggesting that this lectin may play an important role in a-Gal-mediated diseases. In agreement with this idea, a recent study established that DCIR on the surface of mast cells mediates the recognition and uptake of cockroach allergen, which contains the a-Gal epitope on N-glycans, and enhances cockroach/IgE-induced mast cell activation and atopic dermatitis-like inflammation.…”