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Alpha-Gal IgE Panel

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Test Includes

Immunoglobulin E, Total; Alpha-Gal; Beef IgE; Pork IgE; Lamb IgE


Expected Turnaround Time

3 - 4 days


Related Documents


Specimen Requirements


Specimen

Serum


Volume

0.5 mL


Container

Red-top tube or gel-barrier tube


Collection

If a red-top tube is used, transfer separated serum to a plastic transport tube.


Storage Instructions

Room temperature


Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

3 months

Freeze/thaw cycles

Stable x3


Test Details


Use

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


Limitations

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


Methodology

Thermo Fisher ImmunoCAP® Allergen-specific IgE


Additional Information

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 Tick11,13 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


Footnotes

1. Wilson JM, Schuyler AJ, Schroeder N, Platts-Mills TA. Galactose-α-1,3-Galactose: Atypical Food Allergen or Model IgE Hypersensitivity? Curr Allergy Asthma Rep. 2017 Jan;17(1):8.28224342
2. Wilson JM, Platts-Mills TAE. Meat allergy and allergens. Mol Immunol. 2018 Aug;100:107-112.29685461
3. Berg EA, Platts-Mills TA, Commins SP. Drug allergens and food--the cetuximab and galactose-α-1,3-galactose story. Ann Allergy Asthma Immunol. 2014 Feb;112(2):97-101.24468247
4. Tripathi A, Commins SP, Heymann PW, Platts-Mills TA. Delayed anaphylaxis to red meat masquerading as idiopathic anaphylaxis. J Allergy Clin Immunol Pract. May-June 2014;2(3):259-65.24811014
5. Carter MC, Ruiz-Esteves KN, Workman L, Lieberman P, Platts-Mills TAE, Metcalfe DD. Identification of alpha-gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis. Allergy. 2018 May;73(5):1131-1134.29161766
6. Pattanaik D,Lieberman P, Lieberman J, Pongdee T, Keene AT. The changing face of anaphylaxis in adults and adolescents. Ann Allergy Asthma Immunol. 2018 Nov;121(5):594-597.30071303
7. Fischer J, Lupberger E, Hebsaker J, et al. Prevalence of type I sensitization to alpha-gal in forest service employees and hunters. Allergy. 2017 Oct;72(10):1540-1547.28273338
8. Posthumus J, James HR, Lane CJ, Matos LA, Platts-Mills TAE, Commins SP. Initial description of pork-cat syndrome in the United States. J Allergy Clin Immunol. 2013 Mar;131(3):923-925.23352634
9. Wilson JM, Schuyler AJ, Workman L, et al. Investigation into the α-Gal Syndrome: Characteristics of 261 Children and Adults Reporting Red Meat Allergy. J Allergy Clin Immunol Pract. Sep-Oct 2019;7(7):2348-2358.e4.30940532
10. Platts-Mills TAE, Li RC, Keshavarz B, Smith AR, Wilson JM. Diagnosis and Management of Patients with the α-Gal Syndrome. J Allergy Clin Immunol Pract. 2020 Jan;8(1):15-23.e1.31568928
11. Commins SP, Satinover SM, Hosen J, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2009 Feb;123(2):426-433.19070355
12. Maier S, Chung CH, Morse M, et al. A retrospective analysis of cross-reacting cetuximab IgE antibody and its association with severe infusion reactions. Cancer Med. 2015 Jan;4(1):36-42.25296628
13. Steinke JW, Platts-Mills TA, Commins SP. The alpha-gal story: lessons learned from connecting the dots. J Allergy Clin Immunol. 2015 Mar;135(3):589-596; quiz 597.25747720
14. Commins SP, Platts-Mills TA. Allergenicity of carbohydrates and their role in anaphylactic events. Curr Allergy Asthma Rep. 2010 Jan;10(1):29-33.20425511
15. Commins SP, James HR, Kelly LA, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. J Allergy Clin Immunol. 2011 May;127(5):1286-1293.21453959
16. Saleh H, Embry S, Nauli A, Atyia S, Krishnaswamy G. Anaphylactic reactions to oligosaccharides in red meat: a syndrome in evolution. Clin Mol Allergy. 2012 Mar 7;10(1):5.22397506
17. Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008 Mar 13;358(11):1109-1117.18337601
18. Hamsten C, Tran TAT, Starkhammar M, et al. Red meat allergy in Sweden: association with tick sensitization and B-negative blood groups. J Allergy Clin Immunol. 2013 Dec;132(6):1431-1434.24094548
19. Bircher AJ, Hofmeier KS, Link S, Heijnen I. Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a review. Eur J Dermatol. 2017 Feb 1;27(1):3-9.27873733
20. Kennedy JL, Stallings AP, Platts-Mills TA, et al. Galactose-α-1,3-galactose and delayed anaphylaxis, angioedema, and urticaria in children. Pediatrics. 2013 May;131(5):e1545-1552.23569097
21. Arkestål K, Sibanda E, Thors C, et al. Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-α 1,3-galactose. J Allergy Clin Immunol. 2011 Apr;127(4):1024-1028.21376382
22. Commins SP, James HR, Stevens W, et al. Delayed clinical and ex vivo response to mammalian meat in patients with IgE to galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2014 Jul;134(1):108-115.24656556
23. Wolver SE, Sun DR, Commins SP, Schwartz LB. A peculiar cause of anaphylaxis: no more steak? The journey to discovery of a newly recognized allergy to galactose-alpha-1,3-galactose found in mammalian meat. J Gen Intern Med. 2013 Feb;(2):322-325.22815061
24. Apostolovic D, Tran TAT, Hamsten C, Starkhammar M, Velickovic TC, van Hage M. Immunoproteomics of processed beef proteins reveal novel galactose-α-1,3-galactose-containing allergens. Allergy. 2014 Oct;69(10):1308-1315.24942937
25. Mullins RJ, James H, Platts-Mills TAE, Commins S. Relationship between red meat allergy and sensitization to gelatin and galactose-α-1,3-galactose. J Allergy Clin Immunol. 2012 May;129(5):1334-1342.e1.22480538
26. Caponetto P, Fischer J, Biedermann T. Gelatin-containing sweets can elicit anaphylaxis in a patient with sensitization to galactose-α-1,3-galactose. J Allergy Clin Immunol Pract. May-June 2013;1(3):302-303.24565491
27. Fischer J, Eberlein B, Hilger C, et al. Alpha-gal is a possible target of IgE-mediated reactivity to antivenom. Allergy. 2017 May;72(5):764-771.27775867
28. Retterer MKC, Workman LJ, Bacon JR, Platts-Mills TAE. Specific IgE to gelatin as a cause of anaphylaxis to zoster vaccine. J Allergy Clin Immunol. 2018 May;141(5):1956-1957.29361333
29. Stone CA Jr, Hemler JA, Commins SP, et al. Anaphylaxis after zoster vaccine: Implicating alpha-gal allergy as a possible mechanism. J Allergy Clin Immunol. 2017 May;139(5):1710-1713.e2.27986511

References

Binder AM, Commins SP, Altrich ML, et al. Diagnostic testing for galactose-alpha-1,3-galactose, United States, 2010 to 2018. Ann Allergy Asthma Immunol. 2021 Apr;126(4):411-416.e1.33422649
Crispell G, Commins SP, Archer-Hartman SA, et al. Discovery of Alpha-Gal-ContainingAntigens in North American Tick Species Believed to Induce Red Meat Allergy. Front Immunol. 2019 May 17;10:1056.31156631
Platts-Mills TAE, Commins SP, Biedermann T, et al. On the cause and consequences ofIgE to galactose-α-1,3-galactose: A report from the National Institute of Allergy and Infectious Diseases Workshop on Understanding IgE-Mediated Mammalian Meat Allergy. J Allergy Clin Immunol. 2020 Apr;145(4):1061-1071.32057766
Wilson JM, Keshavarz B, Retterer M, et al. A dynamic relationship between two regional causes of IgE-mediated anaphylaxis: α-Gal syndrome and imported fire ant. J Allergy Clin Immunol. 2021 Feb;147(2):643-652.e7.32522461

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