The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose

Commins, Scott P.; James, Hayley R.; Kelly, Libby A.; Pochan, S.L.; Workman, Lisa J.; Perzanowski, Matthew S.; Kocan, Katherine M.; Fahy, John V.; Ng’ang’a, Lucy; Rönmark, Eva; Cooper, Philip J.; Platts-Mills, Thomas A.E.

doi:10.1016/j.jaci.2011.02.019

Cited by 533 publications

(587 citation statements)

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“…When an alpha-gal sensitized individual eats mammalian meat, his/her IgE specific alpha-gal, attached to high affinity receptors on mast cells, binds the antigen, activating release of mediators such as histamine from mast cells that cause hives and anaphylaxis. 3 (Fig. 1) The journey to discovery of IgE alpha-gal started in 2005 when an oncology group in North Carolina noticed an increased incidence of anaphylaxis in patients receiving a newly developed chimeric mouse-human monoclonal antibody, cetuximab.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, the geographic distribution of the cetuximab-induced anaphylaxis correlates with the distribution of the lone star tick, Amblyomma americanum. 3 The lone star tick differs from the blacklegged tick, Ixodes scapularis, known to cause Lyme disease, in that it is much more aggressive in both adult and larvae forms. The larvae ticks are also called seed ticks and their bites are often confused with chigger bites, which come from the larval form of the trombiculid mite.…”

Section: Discussionmentioning

confidence: 99%

“…Long attachment, repeated attachments, and large numbers of larvae bites can all cause elevations of IgE alpha-gal to >100 kU/L. 3 In addition to being a cause for cetuximab-induced anaphylaxis, IgE alpha-gal is now recognized as the cause for meatinduced delayed anaphylaxis. The connection between red meat ingestion and anaphylaxis remained elusive for several reasons: adult-onset food allergy is rare; anaphylaxis was delayed, and the commercially available skin prick test for mammalian meat was negative in the majority of cases.…”

Section: Discussionmentioning

confidence: 99%

“…Since the article in 2009 linking IgE alpha-gal to anaphylaxis from mammalian meat, 4 cases of meat-induced, delayed anaphylaxis have been reported in Texas, Georgia, South Carolina, Mississippi, Kentucky, Oklahoma, West Virginia and Spain, in addition to the original five southeast states. 1,3,9 The alpha-gal story is truly a paradigm-shifting phenomenon for three distinct reasons. First, anaphylaxis occurred with the primary exposure to the glycoprotein cetuximab.…”

Section: Discussionmentioning

confidence: 99%

“…Humans can become sensitized to alpha-gal after tick bites, developing alpha-gal specific IgE that is detected commercially using a solid phase immunoassay. 3 We present three clinical cases to illustrate this new syndrome. In addition, we review the discovery of alpha-gal specific IgE and how it impacts the current approach to anaphylaxis.…”

Section: Introductionmentioning

confidence: 97%

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A Peculiar Cause of Anaphylaxis: No More steak?

et al. 2012

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In recent years, a newly recognized allergic disease has been uncovered, and seemingly idiopathic causes of anaphylaxis now have an explanation. Individuals bitten by the lone star tick may develop IgE antibodies to the carbohydrate galactose-α-1,3-galactose (alphagal). Upon exposure of sensitized subjects to mammalian meat containing alpha-gal on glycoproteins or glycolipids, delayed anaphylaxis may ensue, often three to six hours after ingestion. 1 Many of these individuals have negative allergy skin prick tests to meat, further obscuring the diagnosis. With the recent development of IgE alpha-gal tests, the clinical diagnosis can be confirmed in the laboratory.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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A Peculiar Cause of Anaphylaxis: No More steak?

et al. 2012

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Management of Food Allergies and Food-Related Anaphylaxis

Iglesia,

Kwan,

Virkud

et al. 2024

JAMA

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ImportanceAn estimated 7.6% of children and 10.8% of adults have IgE-mediated food-protein allergies in the US. IgE-mediated food allergies may cause anaphylaxis and death. A delayed, IgE-mediated allergic response to the food-carbohydrate galactose-α-1,3-galactose (alpha-gal) in mammalian meat affects an estimated 96 000 to 450 000 individuals in the US and is currently a leading cause of food-related anaphylaxis in adults.ObservationsIn the US, 9 foods account for more than 90% of IgE-mediated food allergies—crustacean shellfish, dairy, peanut, tree nuts, fin fish, egg, wheat, soy, and sesame. Peanut is the leading food-related cause of fatal and near-fatal anaphylaxis in the US, followed by tree nuts and shellfish. The fatality rate from anaphylaxis due to food in the US is estimated to be 0.04 per million per year. Alpha-gal syndrome, which is associated with tick bites, is a rising cause of IgE-mediated food anaphylaxis. The seroprevalence of sensitization to alpha-gal ranges from 20% to 31% in the southeastern US. Self-injectable epinephrine is the first-line treatment for food-related anaphylaxis. The cornerstone of IgE-food allergy management is avoidance of the culprit food allergen. There are emerging immunotherapies to desensitize to one or more foods, with one current US Food and Drug Administration–approved oral immunotherapy product for treatment of peanut allergy.Conclusions and RelevanceIgE-mediated food allergies, including delayed IgE-mediated allergic responses to red meat in alpha-gal syndrome, are common in the US, and may cause anaphylaxis and rarely, death. IgE-mediated anaphylaxis to food requires prompt treatment with epinephrine injection. Both food-protein allergy and alpha-gal syndrome management require avoiding allergenic foods, whereas alpha-gal syndrome also requires avoiding tick bites.

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α-Gal Syndrome vs Chronic Urticaria

et al. 2019

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Galactose-α-1,3-galactose (α-gal) is an oligosaccharide expressed on glycoproteins and glycolipids of nonprimate mammals and is the causal epitope of an IgE-mediated allergy to mammalian meat. 1,2 First reported in 2009, the α-gal syndrome is an increasingly appreciated problem across the southeastern United States and other parts of the world. 2 It is clear that tick bites, specifically relating to Amblyomma americanum (lone star tick), are causal in many, if not most, cases of α-gal sensitization in the United States. 3 Following sensitization, many individuals will experience allergic symptoms on ingestion of meat or other products (eg, dairy) derived from nonprimate mammals. In contrast to typical IgE-mediated reactions, which occur within minutes of exposure, the α-gal allergy typically has a delayed onset of 2 to 6 hours. 2 The severity of the reaction varies from general urticaria to anaphylaxis, and individuals may not react to every exposure. Because of these atypical features, proper diagnosis can prove challenging. An epidemiological investigation of a pediatric population reported that α-gal may be misdiagnosed as recurrent urticaria or idiopathic anaphylaxis. 4 While a recent report postulated that α-gal syndrome might represent a novel cause of chronic urticaria, further research failed to find such an association. 5,6 Nevertheless, in areas where α-gal sensitization is prevalent, the potential for misdiagnosing cases of α-gal syndrome as chronic urticaria still exists. Here, we report cases labeled as chronic urticaria or chronic idiopathic urticaria within a cohort of patients in central Virginia being evaluated for α-gal syndrome.

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The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose

Cited by 533 publications

References 36 publications

A Peculiar Cause of Anaphylaxis: No More steak?

A Peculiar Cause of Anaphylaxis: No More steak?

Management of Food Allergies and Food-Related Anaphylaxis

α-Gal Syndrome vs Chronic Urticaria

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