Investigation into the α-Gal Syndrome: Characteristics of 261 Children and Adults Reporting Red Meat Allergy

Wilson, Jeffrey M.; Schuyler, Alexander J.; Workman, Lisa J.; Gupta, Monica; James, Hayley R.; Posthumus, Jonathon; McGowan, Emily C.; Commins, Scott P.; Platts-Mills, Thomas A.E.

doi:10.1016/j.jaip.2019.03.031

Cited by 124 publications

(158 citation statements)

References 40 publications

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“…In addition, 3 of the 13 patients had a significant elevation of tryptase, again with timing that matched symptom onset. At a simple level, those results confirmed the timing reported by most patients, 42 because we know that basophils from these patients that have been incubated in vitro with a-Galeexpressing glycoprotein (eg, a-Gal-HSA, cetuximab, or beef thyroglobulin) will activate CD63 within 20 minutes. 43,45 The results argue strongly that the delay reflects the time taken for a relevant form of the antigen to appear in the circulation.…”

Section: Recent Insights Into Food Allergysupporting

confidence: 82%

“…These particles are small enough to pass out of the vasculature into the interstitial tissue of the skin or arterial walls; if these particles still carried the a-Gal epitope they would be ideally placed to activate mast cells in the tissues. In support of this hypothesis, Roman-Carrasco et al 42 recently reported that glycolipid forms of a-Gal, but not glycoproteins, passed through an epithelial barrier model intact and were packaged into chylomicrons. 49 As an extension of this glycolipid hypothesis we have also been interested in the possibility that IgE to a-Gal could be relevant to inflammatory diseases that are not traditionally considered "allergic."…”

Section: Recent Insights Into Food Allergymentioning

confidence: 87%

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α-Gal and other recent findings that have informed our understanding of anaphylaxis

Wilson

Platts-Mills

2020

Annals of Allergy, Asthma & Immunology

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A B S T R A C TObjective: To summarize the current understanding of anaphylaxis, with an emphasis on major findings that have been reported within the last 10 years. Data Sources: Queries relating to anaphylaxis, immunoglobulin E (IgE), and mast cells were conducted with PubMed and Google Scholar, searching for primary articles and review papers. Study Selections: We focused on articles written in English and which were reported in major allergy and immunology journals. Results: Anaphylaxis represents an extreme manifestation of a form of allergic immunity that appears to have evolved to protect against "toxic" threats that present at skin and mucosal barriers. The factors that have contributed to a rise in anaphylaxis are increasingly appreciated to relate to changes in hygiene and microbial ecology that have occurred with industrialization. Induction of allergen-specific IgG4 is often part of the allergic response and is associated with protection against anaphylaxis. The recognition of the a-Gal syndrome suggests that carbohydrates can be epitopes that are relevant to anaphylaxis and that IgEmediated reactions do not always occur "immediately." Conclusion: Our understanding of anaphylaxis has advanced significantly over the past 10 years. It is anticipated that ongoing research will build on this foundation to further advance our knowledge of anaphylaxis and also translate into clinically meaningful therapies.Ó 2019 Published by Elsevier Inc. on behalf of American College of Allergy, Asthma & Immunology. InstructionsCredit can now be obtained, free for a limited time, by reading the review article and completing all activity components. Please note the instructions listed below:Review the target audience, learning objectives and all disclosures.Complete the pre-test.Read the article and reflect on all content as to how it may be applicable to your practice.Complete the post-test/evaluation and claim credit earned. At this time, physicians will have earned up to 1.0 AMA PRA Category 1 Credit TM . Minimum passing score on the post-test is 70%. Overall Purpose Participants will be able to demonstrate increased knowledge of the clinical treatment of allergy/asthma/immunology and how new information can be applied to their own practices.Disclosures: TPM has a patent on an IgE assay to a-Gal and has received assay support from Phadia/Thermo-Fisher; JW has received research support from Phadia/Thermo-Fisher.

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Section: Recent Insights Into Food Allergysupporting

confidence: 82%

Section: Recent Insights Into Food Allergymentioning

confidence: 87%

α-Gal and other recent findings that have informed our understanding of anaphylaxis

Wilson

Platts-Mills

2020

Annals of Allergy, Asthma & Immunology

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“…Red meat allergy (RMA) is an allergic reaction to aGal caused by a hypersensitive IgE response upon recognition of the glycan epitope. Although aGal has been well documented as an elicitor of RMA, the diagnostic test also suffers from sIgE-based assays for false-positive results [50][51][52][53][54][55][56][57]. The aGal allergy is also highly relevant to hyperreactions to xenoplantation [58] and to anti-cancer therapy using the monoclonal antibody cetuximab [59].…”

Section: Agal In the Tick Sg As The Sensitizer Of Red Meat Allergymentioning

confidence: 99%

Alpha-Gal and Cross-Reactive Carbohydrate Determinants in the N-Glycans of Salivary Glands in the Lone Star Tick, Amblyomma americanum

et al. 2020

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Ticks are important ectoparasites and vectors of numerous human and animal pathogens. Ticks secrete saliva that contains various bioactive materials to evade the host defense system, and often facilitates the pathogen transmission. In addition, the Lone star tick saliva is thought to be the sensitizer in red meat allergy that is characterized by an allergic reaction to glycan moieties carrying terminal galactose-alpha-1,3-galactose (aGal). To assess N-glycome of Amblyomma americanum, we examined the N-glycan structures in male and female salivary glands at three different feeding stages and in carcasses of partially fed lone star ticks. We also surveyed the genes involved in the N-glycosylation in the tick species. The aGal epitopes and cross-reactive carbohydrate determinants (CCD) increases over time after the onset of blood feeding in both male and female A. americanum. These CCDs include xylosylation of the core mannose, 1,3-mono and 1,3- and 1,6-difucosylations of the basal GlcNac and mono- or diantennary aGal. Combinations of both xylosylation and aGal and fucosylation and aGal were also found on the N-glycan structures. While the enzymes required for the early steps of the N-glycosylation pathway are quite conserved, the enzymes involved in the later stages of N-glycan maturation in the Golgi apparatus are highly diverged from those of insects. Most of all, we propose that the aGal serves as a molecular mimicry of bioactive proteins during tick feedings on mammalian hosts, while it contributes as a sensitizer of allergy in atypical host human.

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“…Until now, there are a limited number of cases with alpha-Gal allergy in children. 2,3 Avoidance is the mainstay management of food allergies; nevertheless, exclusion of red meat from the diet may be difficult, and the risk of accidental exposure can be high. Satisfying outcomes with oral immunotherapy in several food allergies such as peanut, cow's milk, and hen's egg have been reported.…”

mentioning

confidence: 99%

“…Also, SPT with cetuximab provides a sensitive diagnostic option to evaluate alpha-Gal allergy.There is a single case series report of 45 children and a report with a limited number of pediatric cases with several adult cases with alpha-Gal allergy. 1,3,9,10 It has been presumed that tick bites are the main cause of sensitization to alpha-Gal. Alpha-Gal has been identified in the gastrointestinal tract of the tick species Ixodes Ricinus that appears to be responsible for alpha-Gal allergy in Europe and in our region.…”

mentioning

confidence: 99%

Red meat desensitization in a child with delayed anaphylaxis due to alpha‐Gal allergy

Yücel

Çimen

Varol

et al. 2019

Pediatric Allergy Immunology

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Investigation into the α-Gal Syndrome: Characteristics of 261 Children and Adults Reporting Red Meat Allergy

Cited by 124 publications

References 40 publications

α-Gal and other recent findings that have informed our understanding of anaphylaxis

α-Gal and other recent findings that have informed our understanding of anaphylaxis

Alpha-Gal and Cross-Reactive Carbohydrate Determinants in the N-Glycans of Salivary Glands in the Lone Star Tick, Amblyomma americanum

Red meat desensitization in a child with delayed anaphylaxis due to alpha‐Gal allergy

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