Sensitization to alpha‐gal as a cause of idiopathic anaphylaxis

Background: The cause for anaphylaxis cannot be identiﬁed after extensive evaluation in a large proportion of patients, who are classiﬁed as having ‘idiopathic anaphylaxis’ (IA). As food consumption patterns, genetic background, and environmental factors can lead to diﬀerences in allergen sensitization patterns in diﬀerent regions, we sought to identify the aetiology of IA in cohort of Sri Lankan patients. Methods: Of the patients referred to our clinic following anaphylaxis, 65 were recruited as a cause could not be identiﬁed. The events that led to the episode of anaphylaxis, the triggers, the severity of symptoms and treatment received were recorded and skin prick test, ISAC ImmunoCAP test and serum tryptase was carried out. Results: Of the 65 patients, 42/65 (64.6%) were females and 49/65 (75.38%) were adults. 46/65 (70.8%) had grade II anaphylaxis and 34/65 (52.3%) were found to have speciﬁc IgE to alpha-gal, with symptoms occurring 0.5 to 6 hours since ingestion of food. Of those who had speciﬁc IgE to alpha-gal, 12 (35.3%) had consumed red meat and 10 (29.4%) milk products (3 had consumed fermented buﬀalo milk), before the episode of anaphylaxis. Diﬃculty in breathing, swelling of lips and syncope was signiﬁcantly higher in those who were not sensitized to alpha-gal, while diarrhoea and abdominal pain were more common in those sensitized to alpha-gal, although this was not signiﬁcant. Conclusion: A large proportion of patients presenting with IA were found to be sensitized to alpha-gal, which was the likely cause of their anaphylaxis.

patients whose ISAC was negative, a serum tryptase was done and results were within the normal range.Statistical analysis was done using GraphPad prism version 9.0.
Allergy to Galactose-α-1,3-galactose (α-gal) has been shown as an important cause of anaphylaxis among those in whom a cause is unidentifiable. 6Of the patients sensitized to alpha-gal, fourteen (41.2%) were male and twenty-two (64.7%) were adults.Sixteen (47.1%) did not have detectable IgE to other allergens included in the ISAC ImmunoCAP.Twelve (35.3%) had consumed mammalian meat prior to developing anaphylaxis, and therefore, alpha-gal allergy is most likely to be the trigger in these patients.Fourteen had consumed milk products, and two had consumed gelatine products prior to the reaction.In eight patients, the trigger was unknown or unrelated to alpha-gal.16 of 34 patients who were sensitized had never consumed mammalian meat, as its consumption is less among many ethnic groups in Sri Lanka.Therefore, although they did have specific IgE to alpha-gal possibly following a tick bite, it is unclear if the presence of alpha-gal specific antibodies played a role in causing anaphylaxis in these patients.
Alpha-gal allergy typically occurs 3-6 h after the ingestion of mammalian meat and has been shown to occur due to IgE antibodies specific to the carbohydrate epitope found in mammalian meat. 7Patients reported symptoms between 0.5 and 6 h since ingestion of food.
When considering clinical features, all (34) alpha gal patients reported an average of 2 episodes of anaphylaxis and the others (31) reported an average of 3 episodes at the time of presentation.Urticaria and itching were the most common symptoms in both groups.Difficulty in breathing, swelling of the lips, and syncope were significantly higher (p < 0.05) in those who were not sensitized to alpha-gal.In contrast, diarrhea and abdominal pain were more common in those who were sensitized to alpha-gal, although this was not significant (p > 0.05).
Eleven (16.9%) of all patients with IA were sensitized to cow's milk, and they were also sensitized to alpha-gal.Interestingly, 14 of 34 patients who were found to be sensitized to alpha-gal had consumed milk products and not mammalian meat prior to the reaction.Three of these patients had consumed fermented buffalo milk and not cow's milk.It has been shown in different studies that individuals who are sensitized to alpha-gal react to different types of dairy products, with 70%-90% of individuals with alpha-gal allergy reacting to milk products. 8It was shown that although patients with alpha-gal allergy did not react to the main allergens in cow's milk, they reacted to bovine-γ-globulin, lactoferrin, and lactoperoxidase. 8erefore, it is possible that in the 14 patients with alpha-gal allergy who developed anaphylaxis following the ingestion of milk was due to sensitization to these components in milk.Ten of the fourteen were positive for major cow allergens according to the ISAC Test.-LETTER Two patients developed anaphylaxis following the consumption of gelatine-containing products and were found to have specific antibodies to alpha-gal.Alpha-gal has been reported in gelatinecontaining products, 7 and its presence could have triggered anaphylaxis.Individuals without specific IgE to gelatine but to alphagal have developed anaphylaxis following the administration of vaccines due to the alpha-gal component in gelatine. 9Therefore, it is recommended that gelatine containing vaccines should be administered with caution in those with alpha-gal allergy. 9 summary, a large proportion of patients presenting with IA were found to be sensitized to alpha-gal, which was the likely cause of their anaphylaxis.However, further studies need to be done to ascertain the significance of alpha-gal sensitization among the general Sri Lankan population.

Allergen Number of patients who had specific IgE to a particular allergen (%) Specific IgE mean, [median and range. (ISU-E)]
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© 2023 The Authors.Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.Clin Transl Allergy.2023;e12309.wileyonlinelibrary.com/journal/clt2 - of 4 https://doi.org/10.1002/clt2.12309T A B L E 1 Allergen sensitization pattern among patients who presented with idiopathic anaphylaxis.