Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose

Abstract

Background: Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions.

Objective: We sought to determine whether IgE antibodies to alpha-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb.

Methods: Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens.

Results: Twenty-four patients with IgE antibodies to alpha-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow's milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for alpha-gal.

Conclusion: We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope alpha-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.

FIG 1

Representative SPT and intradermal test results in patients with IgE antibodies to α-gal. A, SPTs were performed on the volar surface of the arm with commercially available skin testing reagents at 1:20 wt/vol after histamine reactivity (denoted by +) was verified. Right column of SPTs: B, beef; C, chicken; L, lamb; P, pork; T, turkey, Co, codfish. Left column of SPTs: DP, Dermatophagoides pteronyssinus; DF, Dermatophagoides farinae; CR, cockroach; C, cat; D, dog; G, grass. B, Intradermal testing was performed with 0.03 mL of a 1:100 dilution of commercially available reagents (ie, 1:2000 wt/vol) with a 25-gauge needle. C, SPTs with commercially available reagents (left) and fresh meat extract (right) in which values in millimeters represent the greatest diameter of wheal response. NR, Nonreactive. The experiments in Fig 1, A and B, were performed on the same patient during a single clinic visit and were measured 15 minutes after placement. Negative controls were 50% glycerin/saline for SPTs and buffered saline for intradermal tests.

FIG 2

A, IgE antibody binding to allergens in serum samples from 24 patients with IgE antibodies to α-gal. The horizontal lines indicate geometric mean values. Numbers below the limit of detection indicate the number of negative values for each allergen. Four results for α-gal were greater than 100 IU/mL and are listed in Table II. One result each for beef, cat, and dog were greater than 100 IU/mL. ‡Chicken, turkey, and fish have a significantly lower prevalence of positive results (P < .01) compared with α-gal, beef, pork, and lamb by means of χ² analysis. Abs, Antibodies. B, Correlation of IgE antibodies to α-gal and IgE antibodies to beef in patients with IgE antibodies to α-gal. C, Correlation of IgE antibodies to cat and IgE antibodies to dog in patients with IgE antibodies to α-gal. D, Correlation of IgE antibodies to cat and IgE to Fel d 1 in patients with IgE antibodies to α-gal.

FIG 3

Absorption of sera with sepharose-bound α-gal or sepharose-bound bovine thyroglobulin (BT). A, Sera from patients (n = 8) with IgE antibodies to α-gal were incubated overnight with α-gal bound to sepharose beads (gray bars), bovine thyroglobulin bound to sepharose beads (red bars), or mock-coupled sepharose beads (blue bars) expressed as specific IgE antibodies and adjusted for transferrin concentration. Error bars indicate 95% CIs. B, Sera from patients (n = 4) with atopic dermatitis (AD) treated as described for Fig 3, A. C, Sera from 2 individual patients with IgE antibodies to α-gal (subjects 18 and 115) and 2 patients with atopic dermatitis (AD1 and AD2) treated as described for Fig 3, A.