Role and Mechanism of Galactose-Alpha-1,3-Galactose in the Elicitation of Delayed Anaphylactic Reactions to Red Meat

Abstract

Purpose of review: The alpha-Gal (α-Gal) syndrome is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-alpha-1,3-galactose (α-Gal). In this article, we review the presence of α-Gal in food and non-food sources; we discuss the evolutionary context of the antibody response to α-Gal and highlight immune responses to α-Gal and other carbohydrates.

Recent findings: IgE antibodies have been associated with delayed allergy to red meat. In addition to food, drugs, and other products of animal origin are increasingly perceived as a risk for patients sensitized to α-Gal. The link between tick bites and anti-α-Gal IgE-antibody production that has been established first by epidemiological studies has now been confirmed in mouse models. The anti-α-Gal immune response is complex and characterized by a unique feature. IgM and IgG antibodies have been found to confer protection against pathogens whereas the IgE-response to α-Gal is detrimental and causes severe reactions upon exposure to mammalian meat and other products.

Keywords: Alpha-gal; Carbohydrate; Food allergy; Red meat allergy; Tick.

Fig. 1

α-Gal syndrome. The α-Gal syndrome describes an IgE-mediated allergy to the disaccharide galactose-α-1,3-galactose (α-Gal). Base arc—tick bites are assumed to be the most frequent and most important primary sensitization source to α-Gal, and α-Gal syndrome is the first allergy classified as tick-borne disease. Left upper arc—administration of drugs derived from mammalian cells and tissue (like cetuximab, antivenom, gelatin in colloids or vaccines) can induce drug allergy. Left lower arc—as part of xeno-rejection, deterioration of biological heart valves is assumed. Right arc—consumption of mammalian muscle meat and innards, but also dairy products, gelatin in sweets or porcine pancreatic enzymes in digestion aids can induce food allergy

Fig. 2

Anti-α-Gal antibodies: friend or foe? It is commonly assumed that IgM and IgG antibodies are generated by continuous stimulation by the intestinal microbiome and probably also by food. Bites of different hard ticks have been associated with the production of IgE antibodies directed to α-Gal. Whereas IgE antibodies are detrimental and responsible for anaphylactic reactions to food and drugs, IgG and IgM antibodies seem to play a role in protection from parasites and possibly other pathogens. The insertion of α-Gal glycolipids into tumor cells has been investigated in pre-clinical models of cancer immunotherapy. A typical α-Gal carbohydrate structure as e.g. present on cetuximab [36] is shown above the antibody. Yellow circle: galactose; green circle: mannose; blue square: N-acetylglucosamine; red triangle: fucose