The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose

Abstract

Background: In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies.

Objectives: We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur.

Methods: Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP.

Results: Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20-fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (χ(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001).

Conclusion: The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.

Fig 1

Time course of IgE antibodies to alpha-gal and total IgE collected as sequential samples following episodes of multiple tick bites (red arrows) in three subjects. The time intervals between samples vary considerably, and the specific times can be seen in Table I. Subjects #1 and #3 experienced episodes of generalized urticaria starting 3-4 hours after eating mutton and beef, respectively (indicated by red asterisk). In each case, this was the first such episode.

Fig 2

Prevalence of IgE antibodies to alpha-gal among 125 patients with or without histories of tick bites. Histories of bites were analyzed by length of time that reactions persisted at the site. Chi square analysis on three bite categories versus assays for IgE antibodies >0.35 IU/ml.

Fig 3

Correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from the tick Amblyomma americanum in 125 sera obtained from patients living in Virginia.

Fig 4

Comparison of the states where anaphylactic reactions to cetuximab were reported in 2006 (A) and the reported prevalence of Rocky Mountain spotted fever (B). Distribution of known cases of patients with delayed anaphylaxis to red meat whose serum contained IgE antibodies to alpha-gal (C). Markers indicate the number of cases: • single cases; smaller black stars indicate 5-24 cases within a state, and larger black stars indicate states with ≥25. Data in panel A from Bristol-Myers Squibb; data in panel B from CDC website. Numbers of cases in states with stars: 65 Arkansas, 14 Georgia, 8 Maryland, 5 Mississippi, 30 Missouri, 35 North Carolina, 25 Oklahoma, 40 Tennessee, >200 Virginia. In panel D, the known distribution of the tick Amblyomma americanum is shown: data from CDC website.