IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4

J Allergy Clin Immunol. 2024 Apr;153(4):1050-1062.e6. doi: 10.1016/j.jaci.2023.12.003. Epub 2023 Dec 21.


Background: Alpha-gal (Galα1-3Galβ1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood.

Objective: We aimed to establish a mouse model of alpha-gal allergy for in-depth immunologic analyses.

Methods: Alpha-galactosyltransferase 1-deficient mice devoid of alpha-gal glycosylations were sensitized with the alpha-gal-carrying self-protein mouse serum albumin by repetitive intracutaneous injections in combination with the adjuvant aluminum hydroxide. The role of basophils and IL-4 in sensitization was investigated by antibody-mediated depletion.

Results: Alpha-gal-sensitized mice displayed increased levels of alpha-gal-specific IgE and IgG1 and developed systemic anaphylaxis on challenge with both alpha-gal-containing glycoproteins and glycolipids. In accordance with alpha-gal-allergic patients, we detected elevated numbers of basophils at the site of sensitization as well as increased numbers of alpha-gal-specific B cells, germinal center B cells, and B cells of IgE and IgG1 isotypes in skin-draining lymph nodes. By depleting IL-4 during sensitization, we demonstrated for the first time that sensitization and elicitation of allergy to alpha-gal and correspondingly to a carbohydrate allergen is dependent on IL-4.

Conclusion: These findings establish IL-4 as a potential target to interfere with alpha-gal allergy elicited by tick bites.

Keywords: Alpha-gal syndrome; GGTA1-deficient mouse model; Galα1-3Galβ1-4GlcNAc; IL-4; IgE; anaphylaxis; food allergy; red meat allergy.

MeSH terms

  • Allergens
  • Anaphylaxis*
  • Animals
  • Food Hypersensitivity*
  • Humans
  • Immunoglobulin E
  • Immunoglobulin G
  • Interleukin-4
  • Mammals
  • Mice
  • Tick Bites*


  • Allergens
  • Immunoglobulin E
  • Immunoglobulin G
  • Interleukin-4
  • IL4 protein, human
  • Il4 protein, mouse

Supplementary concepts

  • red meat allergy