Delayed anaphylaxis to alpha-gal, an oligosaccharide in mammalian meat

Abstract

IgE-mediated hypersensitivity refers to immune reactions that can be rapidly progressing and, in the case of anaphylaxis, are occasionally fatal. To that end, identification of the associated allergen is important for facilitating both education and allergen avoidance that are essential to long-term risk reduction. As the number of known exposures associated with anaphylaxis is limited, discovery of novel causative agents is crucial to evaluation and management of patients with idiopathic anaphylaxis. Within the last 10 years several apparently separate observations were recognized to be related, all of which resulted from the development of antibodies to a carbohydrate moiety on proteins. Interestingly, the exposure differed from airborne allergens but was nevertheless capable of producing anaphylactic and hypersensitivity reactions. Our recent work has identified these responses as being due to a novel IgE antibody directed against a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (“alpha-gal”). This review will present the historical summary of the identification of cetuximab hypersensitivity due to alpha-gal IgE and discuss the non-primate mammalian meat food allergy as well as current goals and directions of our research programs.

Food allergy: immune mechanisms, diagnosis and immunotherapy

“…Another variant of IgE-mediated food allergy occurs in individuals who produce IgE antibodies that are specific for the red meat carbohydrate galactose-α-1,3-galactose, rather than specific for a protein epitope 26 . As patients with this type of food allergy have usually consumed red meat uneventfully for many years, it has been proposed that sensitivity is initiated through tick bites, via exposure to antigens transmitted in the saliva of ticks that have fed on mammals 26 .…”

“…As patients with this type of food allergy have usually consumed red meat uneventfully for many years, it has been proposed that sensitivity is initiated through tick bites, via exposure to antigens transmitted in the saliva of ticks that have fed on mammals 26 . Although these reactions can be severe, they are unlike other IgE-mediated allergic reactions to food in that symptom onset is delayed by 4–6 hours or longer 26,27 .…”

The pathophysiology of anaphylaxis

“…7, 8 In addition to the biphasic reactions observed in some patients with anaphylaxis induced by a variety of causes, patients who have IgE reactive with the oligosaccharide galactose-alpha-1,3-galactose (“alpha-gal”), which is present in mammalian meat and in some therapeutic antibodies, can exhibit anaphylaxis after a delay of several hours during which no signs or symptoms are apparent. 9 …”

The Developmental History of IgE and IgG4 Antibodies in Relation to Atopy, Eosinophilic Esophagitis, and the Modified TH2 Response

“…In some conditions, such as bacterial colonization, or more extreme situations, such as CD4 deficiency, IgE can be produced in the absence of T cell help [35]. These B cells produce “natural” antibodies with a broad specificity and may be the precursors of isotype-switched B cells producing antibodies to glycans such as the antibodies to the galactose-alpha-1,3 galactose epitope [36, 37] and low-molecular compounds such as quaternary ammonium compounds related to muscle relaxants [38, 39] and drugs like pholcodine [40–43]. …”