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

Perusko, Marija, Grundström, Jeanette, Eldh, Maria, Hamsten, Carl, Apostolovic, Danijela, van Hage, Marianne·2024·Frontiers in Immunology
DOI 10.3389/fimmu.2024.1335911PMC PMC10838981
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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.

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Figure 1 Structural resemblance between α-Gal and the blood group B antigen. Regardless of blood type, individuals may develop AGS. However, individuals with blood group B/AB are underrepresented among AGS patients, as the structural similarity between the α-Gal epitope and the blood group B antigen confers protection against developing anti-α-Gal IgE antibodies. In addition, anti-α-Gal IgE antibodies from AGS patients with blood group A or 0 often cross-react with the blood group B antigen. This cross-reactivity is absent in AGS patients with blood group B/AB. Created with BioRender.com.
Figure 1 Structural resemblance between α-Gal and the blood group B antigen. Regardless of blood type, individuals may develop AGS. However, individuals with blood group B/AB are underrepresented among AGS patients, as the structural similarity between the α-Gal epitope and the blood group B antigen confers protection against developing anti-α-Gal IgE antibodies. In addition, anti-α-Gal IgE antibodies from AGS patients with blood group A or 0 often cross-react with the blood group B antigen. This cross-reactivity is absent in AGS patients with blood group B/AB. Created with BioRender.com.CC BY · PubMed Central
Figure 2 α-Gal carrying glycoproteins identified so far from innards, beef, milk, sweets, pharmaceuticals, and ticks. Created with BioRender.com.
Figure 2 α-Gal carrying glycoproteins identified so far from innards, beef, milk, sweets, pharmaceuticals, and ticks. Created with BioRender.com.CC BY · PubMed Central

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Citations

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Metadata

Authors
Perusko, M., Grundström, J., Eldh, M., Hamsten, C., Apostolovic, D., & van Hage, M.
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2024-01-22
Volume
15
ISSN
1664-3224
DOI
10.3389/fimmu.2024.1335911
PMC
PMC10838981
Cited by
52
References
4
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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