Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose

Chung, Christine H.; Mirakhur, Beloo; Chan, Emily; Le, Quynh Thu; Berlin, Jordan; Morse, Michael; Murphy, Barbara A.; Satinover, S.M.; Hosen, Jacob D.; Mauro, David; Slebos, Robbert J.C.; Zhou, Qinwei; Gold, Diane R.; Hatley, Tina; Hicklin, Daniel J.; Platts-Mills, Thomas A.E.

doi:10.1056/nejmoa074943

Cited by 1,353 publications

(1,167 citation statements)

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“…Consequently, delayed meat allergy is not a consequence of oral but cutaneous sensitization to the α‐gal epitope expressed on proteins present in the gastrointestinal tract of these arthropods 27. Thereafter, individuals may develop allergic reactions due to IgE reactivity with α‐gal on mammalian proteins, for example murine and feline Ig 16, 24, 28. This pathophysiology is reminiscent of other, so‐called secondary food allergies, for example birch pollen‐related food allergy.…”

Section: Discussionmentioning

confidence: 99%

The quantity and quality of α-gal-specific antibodies differ in individuals with and without delayed red meat allergy

Kollmann

Nagl

Ebner³

et al. 2016

Allergy

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BackgroundIgG to galactose‐α‐1,3‐galactose (α‐gal) are highly abundant natural antibodies (Ab) in humans. α‐Gal‐specific IgE Ab cause a special form of meat allergy characterized by severe systemic reactions 3–7 h after consumption of red meat. We investigated 20 patients who experienced such reactions and characterized their α‐gal‐specific IgE and IgG responses in more detail.Methodsα‐Gal‐specific IgE was determined by ImmunoCAP. IgE reactivity to meat extract and bovine gamma globulin (BGG) was assessed by immunoblotting and ELISA, respectively. In some experiments, sera were pre‐incubated with α‐gal or protein G to deplete IgG Ab. α‐Gal‐specific IgG1–4 Ab in individuals with and without meat allergy were assessed by ELISA.ResultsIn immunoblots, BGG was the most frequently recognized meat protein. Binding of IgE and IgG to BGG was confirmed by ELISA and completely abolished after pre‐incubation with α‐gal. Neither the depletion of autologous α‐gal‐specific IgG Ab nor the addition of α‐gal‐specific IgG Ab from nonallergic individuals changed the IgE recognition of BGG of meat‐allergic patients. Meat‐allergic patients showed significantly higher α‐gal‐specific IgG1 and IgG3 Ab than nonallergic individuals, whereas the latter showed significantly higher levels of α‐gal‐specific IgG4 Ab.ConclusionPatients with delayed meat allergy display IgE and IgG Ab that selectively recognize the α‐gal epitope on BGG. Their enhanced α‐gal‐specific IgE levels are accompanied by high levels of α‐gal‐specific IgG1 devoid of IgE‐blocking activity. This subclass distribution is atypical for food allergies and distinct from natural α‐gal IgG responses in nonallergic individuals.

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Section: Discussionmentioning

confidence: 99%

The quantity and quality of α-gal-specific antibodies differ in individuals with and without delayed red meat allergy

Kollmann

Nagl

Ebner³

et al. 2016

Allergy

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“…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. 2,4 Cetuximab is an antibody against epidermal growth factor receptor, and is used to treat colorectal, head and neck cancers. Patients who developed anaphylaxis did so within minutes of receiving their first intravenous infusion of cetuximab.…”

Section: Discussionmentioning

confidence: 99%

“…However, patients receiving cetuximab developed anaphylaxis after the first exposure. 2 To explain the reaction after initial exposure, Chung, et al found that IgE antibodies against cetuximab were present before the first exposure to the chimeric antibody. 2 This IgE was specific for alpha-gal, an oligosaccharide present on the Fab portion of the cetuximab heavy chain.…”

Section: Discussionmentioning

confidence: 99%

“…2 To explain the reaction after initial exposure, Chung, et al found that IgE antibodies against cetuximab were present before the first exposure to the chimeric antibody. 2 This IgE was specific for alpha-gal, an oligosaccharide present on the Fab portion of the cetuximab heavy chain. 5 Alpha-gal is a carbohydrate found on non-primate mammal and tick glycoproteins, but is not made by humans.…”

Section: Discussionmentioning

confidence: 99%

“…However, research conducted at the University of Virginia by Platts-Mills and colleagues has uncovered a paradigm-changing new class of adult-onset mammalian meat-induced delayed anaphylaxis. 2 Alpha-gal is a carbohydrate moiety found in mammalian meat. Humans can become sensitized to alpha-gal after tick bites, developing alpha-gal specific IgE that is detected commercially using a solid phase immunoassay.…”

Section: Introductionmentioning

confidence: 99%

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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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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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Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose

Cited by 1,353 publications

References 25 publications

The quantity and quality of α-gal-specific antibodies differ in individuals with and without delayed red meat allergy

The quantity and quality of α-gal-specific antibodies differ in individuals with and without delayed red meat allergy

A Peculiar Cause of Anaphylaxis: No More steak?

Management of Food Allergies and Food-Related Anaphylaxis

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