The alpha-gal story: lessons learned from connecting the dots

J Allergy Clin Immunol. 2015 Mar;135(3):589-96; quiz 597. doi: 10.1016/j.jaci.2014.12.1947.

Abstract

Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal, and therefore establishing its cause is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal). IgE to alpha-gal has been associated with 2 distinct forms of anaphylaxis: (1) immediate-onset anaphylaxis during first exposure to intravenous cetuximab and (2) delayed-onset anaphylaxis 3 to 6 hours after ingestion of mammalian food products (eg, beef and pork). Results of our studies and those of others strongly suggest that tick bites are a cause, if not the only significant cause, of IgE antibody responses to alpha-gal in the southern, eastern, and central United States; Europe; Australia; and parts of Asia. Typical immune responses to carbohydrates are considered to be T-cell independent, whereas IgE antibody production is thought to involve sequential class-switching that requires input from T cells. Therefore, establishing the mechanism of the specific IgE antibody response to alpha-gal will be an important aspect to address as this area of research continues.

Keywords: Anaphylaxis; delayed reaction to red meat; galactose-alpha-1,3-galactose.

Publication types

  • Review

MeSH terms

  • Allergens / immunology
  • Anaphylaxis / chemically induced
  • Anaphylaxis / diagnosis
  • Anaphylaxis / immunology*
  • Anaphylaxis / physiopathology
  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Agents / adverse effects
  • Cattle
  • Cetuximab
  • Disaccharides / immunology*
  • Epitopes / immunology
  • Food Hypersensitivity / diagnosis
  • Food Hypersensitivity / immunology*
  • Food Hypersensitivity / physiopathology
  • Humans
  • Hypersensitivity, Delayed / diagnosis
  • Hypersensitivity, Delayed / immunology*
  • Hypersensitivity, Delayed / physiopathology
  • Immunoglobulin E / blood
  • Meat*
  • Swine
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Tick Bites / diagnosis
  • Tick Bites / immunology*
  • Tick Bites / physiopathology

Substances

  • Allergens
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Disaccharides
  • Epitopes
  • galactosyl-(1-3)galactose
  • Immunoglobulin E
  • Cetuximab