Galactose-Alpha-1,3-Galactose (Alpha-Gal), IgE, Serum

Serum

0.2 mL

0.1 mL (Note: This volume does not allow for repeat testing.)

Red-top tube or gel-barrier tube

Measurement of IgE to galactose alpha-1,3-galactose (α-Gal sIgE) is used in the differential diagnosis of α-Gal mediated allergy.^1,2 There are two distinct forms of this allergy: the first is an immediate-onset anaphylaxis observed following intravenous infusion of Cetuximab, a monoclonal antibody against epidermal growth factor receptor, and the second is a delayed-onset allergy or anaphylaxis that occurs several hours following consumption of red meat.³ Bites from certain ticks, such as the Lone Star Tick in the United States, have been implicated in the development α-Gal allergy. Furthermore, α-Gal may be helpful in elucidating the allergen responsible in patients initially diagnosed as having ‘idiopathic’ anaphylaxis or urticaria.^4-6

Although the use of component IgE testing may enhance the evaluation of potentially allergic individuals over the use of whole extracts alone, it cannot yet replace clinical history and oral food challenge in most cases. Clinical history, patient’s age, and presence of comorbidities (such as atopic dermatitis) must be incorporated into the diagnostic determination.

If a food is tolerated in the patient’s diet on a regular basis, detectable food specific IgE does not confirm allergy to that food. In population studies, many individuals produce IgE to α-Gal but do not have allergic symptoms.⁷ If allergy to a specific food is suspected based on clinical history, an undetectable food specific IgE does not exclude allergy to that food.

Alpha-gal allergies are similar to pork-cat syndrome. Pork-cat syndrome usually elicits an immediate allergic response, while a true α-Gal allergy typically features a delayed allergic reaction of 3 to 8 hours after ingestion of the allergen.⁸

Total IgE levels are of value in assessing potential α-Gal allergy because some cases are non-atopic and have low total IgE.^9,10

Thermo Fisher ImmunoCAP® Allergen-specific IgE

In early studies of patients treated with Cetuximab, it was observed that up to 15 percent of patients reacted upon first exposure with severe and sometimes fatal anaphylaxis.^11,12 Further analysis revealed that most of the affected patients lived in the southeast region of the United States and that many of these patients later also reacted to the ingestion of red meat.^11,13-16 These findings led to the identification of α-Gal sIgE as the potentiating factor.¹⁷ Epidemiological data revealed that bites by the tick Amblyomma americanum or Lone Star Tick^11,13 in the USA, later also by Ixodes species in other continents,¹⁸ resulted in sensitization to α-Gal.

While the prevalence of allergy to α-Gal in the United States is not fully known,^18,19 researchers have observed that it occurs mostly in people living in the Southeast region of the United States and certain areas of New York, New Jersey and New England.^11,14,19 It is unclear exactly how the tick bites induce the production of α-Gal sIgE, but a correlation with a history of multiple bites and persistent local reactions has been reported.^15,20 Efforts to understand the physiology of this syndrome are confounded by the fact that African patients with parasitic disorders and a high prevalence of α-Ga sIgE positivity appear not to suffer from any allergic consequences.²¹

The discovery of α-Gal allergy occurred only recently, in large part, because of the unique nature of this syndrome. In contrast to the typical rapid onset of most food allergies, a typical α-Gal sIgE mediated allergic reaction has a delayed onset, occurring 3 to 8 hours after the consumption of the food.²² This lack of chronologic proximity of the reaction to the ingestion of the causative agent has led many of these cases to be wrongly considered as idiopathic anaphylaxis in the past.^4-6 After the delayed onset, the allergic response to α-Gal is similar to that seen for other IgE-mediated food; hives, angioedema, gastrointestinal upset, and possible anaphylaxis. Respiratory distress associated with α-Gal allergy can be particularly harmful to those with asthma.²³ In some patients, cofactors such as exercise and alcohol have been implicated as contributing factors.

α-Gal is a carbohydrate present on glycoproteins in non-primate mammals and certain invertebrates, but not in humans, Old World monkeys or apes.²² It is not expressed in poultry, seafood, and fish. α-Gal is present in many mammalian foods, including meat, internal organs (such as kidney or tripe), milk and other dairy, and gelatin.^24,25 Allergic reaction after ingestion of sweet gums containing gelatins (e.g. Haribo®) have been reported.²⁶ α-Gal is present in the anticancer drug cetuximab, intravenous fluid replacements Gelofusine and Haemaccel, anticoagulant drugs derived from porcine intestine and in replacement heart valves derived from porcine tissue.^17,25,27-29

α-Gal IgE levels greater than or equal to 2.0 IU/ml or >2% of the total IgE makes the diagnosis very likely.¹⁰