Mechanisms of allergy and clinical immunology
The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose

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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 (χ2 = 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 (rs = 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.

Section snippets

Clinic populations in Virginia

Patients presenting to clinic in Charlottesville for evaluation of recurrent anaphylaxis or severe urticarial reactions (n = 121), asthma (n = 56) or control subjects (n = 40) were enrolled and provided serum. Of these, the most recently enrolled 125 subjects responded to a full questionnaire, including questions about tick bites (see Fig E1 in this article’s Online Repository at www.jacionline.org). Patients who specifically presented with urticarial or anaphylactic reactions were enrolled as

Rapid development of IgE antibodies to α-gal after tick bites in 3 subjects

Over the last 3 years, we have had the opportunity to follow serum IgE responses prospectively in 3 subjects whose sera were available from before they experienced multiple tick bites. In each case IgE antibody levels to alpha-gal increased more than 20-fold after tick bites, and there was a parallel, although not identical, increase in total IgE levels (Fig 1). Furthermore, 2 of these subjects (nos. 1 and 3 in Fig 1 and Table I) experienced an episode of generalized urticaria 3 to 4 hours

Discussion

The results presented here strongly suggest that tick bites are a cause, if not the only significant cause, of IgE antibody responses to alpha-gal in the southeastern United States. This evidence includes following the response prospectively in 3 cases, a strong correlation with histories of tick bites, epidemiologic evidence that these antibodies are not found in regions where tick bites are rare, and correlation with IgE antibodies specific for tick proteins. As recently as January 2006, we

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    • Cited by (0)

    Supported by National Institutes of Health grant RO1 AI-20565, AI-AADCRC-U19-070364, K08 AI085190, R21 AI087985, and the Wellcome Trust 072405/Z/03/Z (to P. J. C.).

    Disclosure of potential conflict of interest: S. P. Commins is a volunteer committee member for the American Association of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology and is an author for Up-to-Date. M. S. Perzanowski receives research support from the National Institutes of Health (NIH) and is a member of the AAAAI. J. V. Fahy receives research support from the NIH. P. J. Cooper receives research support from Wellcome Trust. T. A. E. Platts-Mills receives research support from Phadia and the NIH and has a patent on an assay. The rest of the authors have declared that they have no conflict of interest.

    ∗

    These authors contributed equally to this work.

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