Alpha galactose syndrome T78.2

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 16.07.2023

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Alpha Galactose Syndrome; Alpha Gal Syndrome; delayed type meat allergy; Meat allergy

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Delayed immediate type allergy to the disaccharide galactose-alpha-1-3-galactose (alpha-gal), a terminal glycoylation motif in glycoproteins and glycolipids of mammalian cells and tissues. In higher primates as well as in humans, this glycoside motif is no longer expressed due to evolution.

Alpha-Gal syndrome represents a new class of food allergies. It is counted among the summation anaphylaxis. The symptoms occur as a dose- and cofactor-dependent threshold phenomenon (cofactors can be exertion, non-steroidal anti-inflammatory drugs, alcohol, stress and infections). Thus, anaphylactic reactions do not occur after every contact with allergens, but only in the summation of different cofactors.

Typical is the latency of the allergic reaction of several hours (cause: the necessary digestive process of the meat in which alpha-gal is first released), which can last up to several hours. Immediate allergic reactions only occur with intravenous application of alpha-galactose-containing drugs(cetuximab, colloid solutions containing gelatine, e.g. Gelafundin®).

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All mammals, except humans and Old World monkeys, express the disaccharide galactose-alpha 1,3-galactose (alpha-Gal), which is glycosidically linked to proteins and various lipids. It is glycosidically linked to proteins and various lipids. The alpha-Gal epitope is not present in birds, reptiles, and fish.

Tick bites as a co-factor: The prevalence of sensitization to alpha-Gal varies widely by region. It amounted to e.g. in versch. US states (e.g. Arkansas, Tennessee, North Carolina) up to 20% (high tick colonization). In contrast, in California the rate is < 1%. Thus, a local environmental factor is postulated. One of these factors is thought to be bite events by the tick Amblyomma americanum (contains salivary products containing alpha-glactose) in the American collective. Clinically, antibodies against alpha-galactose are suspected when a strong and long persisting (>14 days) inflammatory reaction occurs after tick bites. Apparently, the factor "tick bite" also seems to play a role in European collectives (see casuistry).

Blood groups O and A as a risk factor (?): Another risk factor seems to be the blood group affiliation. For example, a study (Cabezas-Crus A et al. 2017) found that people with blood group B produce fewer alpha-Gal IgE antibodies than people with other blood groups. They are apparently more immune tolerant than people with blood groups 0 and A. The explanation given is that the blood group B antigen contains a fucosylated galactose-alpha-1,3-galactose structure.

Clinical features
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Nausea, diarrhoea, vomiting; intermittent urticaria possibly angioedema. Severe anaphylaxis possible after intravenous application of alpha-galactose-containing drugs (see above).

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Clinic: Patients suffering from unexplained anaphylactic reactions to mammalian meat (see below meat allergy), gelatine, possibly milk (but not to poultry and fish) for years.

Latency period of several hours between meat consumption and allergic symptoms.

Anaphylactic reaction during intravenous application of cetuximab.

Serological evidence of antibodies to alpha-gal.

Positive prick or intradermal test in an alpha-galactose-containing protocol (Gelafundin®).

Rub test (or prick to prick test) with red meat is negative!

Exposure test under clinical control.

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Alpha-galactose-sensitized patients may respond to the intravenous administration of cetuximab with severe anaphylaxis. Cetuximab is produced in mammalian cell lines (mainly mouse, hamster). During antibody production, glycolisation by alpha-Gal at the Fab end of the heavy chain of the chimeric monoclonal antibody may occur. This causes the allergenicity. For other chimeric antibodies such as rituximab, the expression of alpha-Gal has not yet been detected.

Alpha-Galactose in other drugs: Alpha-Galactose is found in colloidal solutions containing gelatine (these can be used for intradermal painting (Gelafundin®). Furthermore, alpha-galactose is found in various vaccines with animal ingredients from cattle or pigs (BCG-Medac ® Instillation, Rapipur® rabies vaccine, Repavex®, Varilrix®, Varivx®, Zostavax® (Wedi R 2017).

Alpha-galactose in medical devices: animal heart valves

All mammals, except humans and primates, produce alpha-gal, which is not present in birds, reptiles and fish (their meat can be eaten by allergy sufferers).

Case report(s)
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Medical history: A 65-year-old patient, who was active as a hunter for many years, has reported daily nausea, diarrhea and intermittent urticaria for several years. The symptoms begin already in the early morning hours. However, they regularly occur a few hours after meals. With increased physical exertion, the symptoms appear more intense and earlier. Therefore, he already refrains from his midday walk.

For many years he has avoided milk and offal. When he consumes milk he feels nauseous. Anaphylactic reactions have repeatedly occurred with offal.

As a hunter he was regularly bitten by ticks. Recently, he noticed that the local reactions of the tick bites were increasingly stronger; in contrast to the past, they persisted for more than 14 days.

Serology: IgE: 130 IU/ml; positive reactions to alpha-Gal (CAP cl.3), beef (CAP cl.3), pork (CAP cl.2) and milk (CAP cl.2) are detectable. No sensitization could be detected with the total extracts. Prick test: positive reaction to cetuximab.

Therapy: elimination diet (red meat, food containing gelatine, dairy products). Poultry and fish were allowed. Among them completely free of symptoms.

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  1. Arkestål K et al (2011) Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-a1,3-galactose. J Clin Immunol 127:1024-1028.
  2. Cabezas-Cruz A et al(2017) Prevalence of type I sensitization to alpha-gal in forest service employees and hunters: Is the blood type an overlooked risk factor in epidemiological studiesof
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  3. Chung CH et al (2008) Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-alpha-1,3- Galactose. New Engl J Med 358:1109-1117.
  4. Commins S et al (2009) Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. Journal of Allergy and Clin Immunol. 123:426-433.
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  8. Weins AB et al.(2016) Special features in the diagnosis and management of alpha-Gal syndrome. Allergo J int 25: 251-255
  9. Wolver S et al(2012) 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 Int Med 28:322-325.


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Last updated on: 16.07.2023