Contribution of alpha-Gal carrying lipids and proteins to red meat allergy

Published: April 19, 2022

α-Gal syndrome, also commonly called ‘red meat allergy’ is characterized by delayed onset of symptoms occurring up to several hours after the ingestion of mammalian meat. In this form of allergic disease, IgE-antibodies are not directed against an animal protein, but to a sugar molecule, galactose-α-1,3-galactose (α-Gal), present in tissues and meat of non-primate mammals. α-Gal has been shown to be present in dairy products, meat and innards, whereby allergic symptoms upon ingestion of innards are more severe and occur more rapidly, although still with a delay of 1-3 hours. In contrast, subcutaneous or intravenous administration of pharmaceutical products containing α-Gal to a patient affected by the α-Gal syndrome results in an immediate allergic reaction, suggesting that the delayed reaction to meat might be related to the digestion process and to the availability of the allergen after breakdown and absorption in the intestine. Although bovine and porcine proteins were shown to carry the carbohydrate α-Gal, prevailing hypotheses favor the idea that α-Gal carried by lipids, e.g., in meat fat, triggers the allergic symptoms as their slow breakdown may coincide with symptom appearance.
In a recent article in The Journal of Allergy and Clinical Immunology (JACI), Chakrapani et al. investigate meat proteins and lipids carrying α-Gal, their respective abundance in meat and their allergenic potency. In a first step, the team analyzed α-Gal carrying glycolipids isolated from rabbit erythrocytes, a source known to be very rich in α-Gal. They characterized the sugar structures on these glycolipids and compared their IgE-binding to a human protein engineered to carry α-Gal. Both glycolipids and glycoproteins were able to bind IgE-antibodies and to stimulate cells from patients with α-Gal syndrome, confirming that the sugar molecule can cause an allergic reaction, irrespective of the carrier molecule.

Next, the authors extracted proteins and lipids from natural food sources, namely beef as the most prevalent trigger of symptoms, and pork kidney, the most potent allergen source. IgE-binding assays and cellular stimulation tests confirmed that α-Gal carrying proteins are much more abundant in pork kidney than in beef, and that they are also more abundant than α-Gal carrying lipids. As proteins carrying α-Gal are more abundant than lipids, it has to be assumed that they are a major trigger of the symptoms. But how can proteins elicit symptoms after several hours? To answer this question, the authors analysed the digestion of pork kidney proteins in an in-vitro gastric and intestinal digestion model. α-Gal carrying proteins were of high molecular weight and they survived a gastric digestion of 2 hours. It was only in the intestinal digestion phase that a slow degradation of the α-Gal carrying proteins was initiated, suggesting that it is the high stability of α-Gal carrying proteins in pork kidney that is responsible for the appearance of allergic symptoms hours after ingestion of meat.

These findings suggest a major role of glycoproteins in delayed anaphylaxis to mammalian meat. They also support the hypothesis that delayed symptoms are related to the late absorption of the allergen, irrespective of the nature of the α-Gal-carrying molecule, glycolipid or glycoprotein. It is to be expected that the relative abundance of α-Gal epitopes and the stability of glycolipids and glycoproteins in the respective foods will most likely determine the relevant trigger molecules in α-Gal syndrome.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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