Galactose-α-1,3-Galactose: Atypical Food Allergen or Model IgE Hypersensitivity?

Abstract

Purpose of Review Galactose-α-1,3-galactose (α-gal) is a carbohydrate allergen with several unique characteristics. In this article, we discuss some recent advances in our understanding of the ‘alpha-gal syndrome,’ highlight data supporting the role of ticks in pathogenesis, and speculate on immune mechanisms that lead to sensitization. Recent Findings First described as the target of IgE in individuals suffering immediate hypersensitivity reactions to the novel anti-EGF monoclonal antibody cetuximab, it is now clear that α-gal sensitization is associated with mammalian meat allergy as well as reactions to other mammalian products. Unlike traditional IgE-mediated food allergies, reactions to α-gal often do not manifest until several hours following an exposure, although co-factors can influence the presentation. Multiple pieces of evidence, including recent work with a mouse model, point to the fact that sensitization is mediated by exposure to certain hard ticks and increasingly we are aware of its globally widespread impact. Summary The oligosaccharide α-gal represents a novel allergen with several unusual clinical features. It has been recognized now on multiple continents and its clinical presentation can be quite variable. Moreover, efforts to delineate the mechanisms leading to α-gal sensitization may have ramifications for our broader understanding of type 2 immunity.

Parasites and allergy: Observations from Africa

“…The first being anaphylactic reactions following the infusion of the monoclonal antibody cetuximab among cancer patients undergoing therapy in the Southeastern United States and the second being delayed‐onset reactions hours after mammalian meat product consumption . Reactions to α‐gal have been documented from the Southeastern US, Central America, Australia and East Asia . A history of tick‐bite exposure has been shown to be strongly correlated with high levels of IgE to α‐gal .…”

“…66 Generally, IgE to CCDs are not thought to be biologically active, but in recent years, responses to the mammalian carbohydrate epitope galactoseα-1,3-galactose (α-gal) have been of interest in the field of allergy since this epitope has been linked to two forms of anaphylaxis. 67 The first being anaphylactic reactions following the infusion of the monoclonal antibody cetuximab among cancer patients undergoing therapy in the Southeastern United States 68 and the second being delayed-onset reactions hours after mammalian meat product consumption. 69 Reactions to α-gal have been documented from the Southeastern US, Central America, Australia and East Asia.…”

“…69 Reactions to α-gal have been documented from the Southeastern US, Central America, Australia and East Asia. 67 A history of tick-bite exposure has been shown to be strongly correlated with high levels of IgE to α-gal. 70 Specific tick species worldwide have been implicated in the induction of IgE to α-gal such as the lone star tick (Amblyomma americanum) in the Southeastern United States, 64 the castor bean tick (Ixodes ricinus) in Sweden, 71 the Australian paralysis tick (Ixodes holocyclus) in Australia 72 and the cattle tick (Haemaphysalis longicornis) in Japan.…”

Food allergy phenotypes: The key to personalized therapy

“…The production of sIgE has been linked to bites from ecto‐parasitic ticks, especially those of the Lone Star tick, Amblyomma americanum . FA by sensitization to alpha‐gal is characterized by delayed‐onset anaphylaxis (ie 3‐6 hour) after ingestion of mammalian food products (eg beef and pork meat; milk; gelatin) . Observations have been recorded in children .…”

“…FA by sensitization to alpha-gal is characterized by delayed-onset anaphylaxis (ie 3-6 hour) after ingestion of mammalian food products (eg beef and pork meat; milk; gelatin). 46 Observations have been recorded in children. 47 60 or to PR10 allergen.…”