Anaphylaxis to the carbohydrate side chain alpha-gal

Area of Science:

• Immunology
• Allergology
• Pharmacology

Background:

• Monoclonal antibody cetuximab use can trigger severe hypersensitivity reactions.
• Such reactions were observed during initial infusions in the southeastern US in 2007.
• These reactions were investigated for underlying causes.

Purpose of the Study:

• To investigate the cause of severe hypersensitivity reactions to cetuximab.
• To identify specific antibodies responsible for these reactions.
• To explore the link between these antibodies and other allergic conditions.

Main Methods:

• Analysis of pretreatment sera from patients experiencing hypersensitivity.
• Testing for immunoglobulin E (IgE) antibodies against specific oligosaccharides.
• Correlation of findings with known allergens and exposure sources.

Main Results:

• Pretreatment sera contained IgE antibodies against galactose-alpha-1,3-galactose (alpha-gal).
• Alpha-gal is present on the cetuximab antibody and is a nonprimate mammalian blood group substance.
• These IgE antibodies are also implicated in delayed anaphylaxis to red meat.

Conclusions:

• The presence of IgE against alpha-gal is a likely cause of cetuximab-induced hypersensitivity.
• Tick bites, particularly from Amblyomma americanum, are identified as the primary source for developing these IgE antibodies.
• Understanding this link is crucial for managing cetuximab therapy and diagnosing red meat allergy.