Carbohydrate moieties are frequently encountered in food and can elicit IgE responses. The recent work has identified a novel IgE antibody response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (α-Gal). IgE antibodies to galactose-α-1,3-galactose are capable of eliciting serious, even fatal, reactions. Alpha-Gal is a blood group substance of nonprimate mammals, a carbohydrate commonly expressed on a large number of nonprimate mammalian proteins. Some of the patients with positive skin tests to cat allergens have IgE antibodies specific for an oligosaccharide on cat IgA. The dominant human IgE epitope on cat IgA2 is the carbohydrate α-Gal. The oligosaccharide α-Gal is also present on the F(ab′)2 part of the monoclonal antibody cetuximab used in biological therapy for cancer. The immunoglobulin E (IgE) antibody response to the carbohydrate Galα1–3Galβ1–4GlcNAc-R is associated with allergies to red meat, cetuximab, and gelatin. The relationship between the exposure to an antigen and the subsequent allergic symptoms is usually obvious. However, two different and novel forms of anaphylaxis have now been associated with IgE to α-Gal, first of them being characterized by delayed onset of symptoms: (1) Delayed-onset anaphylaxis occurs 3 to 6 hours after ingestion of mammalian food products – meat (e.g. beef, pork, or lamb), organs, gelatin or milk of the animals that carry this oligosaccharide. The characteristic features of the syndrome of delayed anaphylaxis to red meat (DARM) are late onset of urticarial (hives), anaphylactic episodes, or angioedema, together with no immediate cause, a history of pruritic tick bites, and exposure to red meat 3 to 6 hours before the onset of symptoms. (2) This epitope has, in addition, been demonstrated to be responsible for potentially life-threatening anaphylactic reactions to cetuximab in patients who have specific IgE antibodies to α-Gal; in these patients, immediate-onset anaphylaxis during first exposure to intravenous cetuximab has been described. Although IgM, IgA and IgG antibodies to α-Gal (anti-α-Gal or anti-Gal) are widely expressed in humans, IgE anti-α-Gal antibodies are not. There is now extensive evidence that the primary impulse to start production of these IgE antibodies is a tick bite or parasitic infestation. The association between tick bites, red meat allergy and IgE to alpha-Gal has been reported from four continents to date. On the other hand, anti-α-Gal IgG and IgM antibodies could contribute to opsonization or blocking of α-Gal motifs on tick proteins, avoiding or reducing development of detrimental anti-α-Gal IgE response. Current evidence suggests that screening for IgE antibodies against the α-Gal epitope may help to identify patients who are at risk of anaphylaxis, including patients who start cetuximab treatment. Areas of investigation: Immunology, Allergology, Immune Response, Biological Therapy, Oncology
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