Relationships between cetuximab-induced anaphylaxis and specific antibodies against allergen and tick-transmitted infections

Background: The principal antigen responsible for cetuximab-induced anaphylaxis is galactose-alpha-1,3-galactose (alpha-gal), expressed on the Fab portion of the monoclonal antibody. Recent studies have shown that cetuximab allergy is associated with a history of tick bite. We explored factors predicting cetuximab-induced anaphylaxis, focusing on the relationship thereof to a history of tick bite. Methods: Fifty-two patients prescribed cetuximab at Ehime University Hospital or Shikoku Cancer Center were included in this study. We measured specific immunoglobulin E (IgE) levels targeting red meats, animal danders, and alpha-gal using immunoCAP. Anti-Rickettsia japonica antibody levels were assayed using an indirect immunoperoxidase test. Anticetuximab antibody was quantified by Western blotting and enzyme-linked immunosorbent assay of serum samples. Results: Of the 52 patients, five exhibited anaphylactic reactions to cetuximab that were not associated with specific IgEs against beef, pork, or animal dander. IgE against agal was detected at class 1 in the sera of two of the five patients. Anticetuximab IgE was detected in four of 52 patients, only one of whom had anaphylaxis to cetuximab. Only two of the 52 patients had a history of a tick bite, one of whom had cetuximab-induced anaphylaxis. The patient without anaphylaxis was positive for anti-R. japonica antibody. Conclusions: The a-gal-specific IgE-positivity can be used to identify those at risk of cetuximab-induced anaphylaxis. The cutoff level should be set up the detection limit to predict cetuximab-induced anaphylaxis, because the antibody levels are very low in our study.