Basophil Activation Test Differentiates Between Patients with Alpha-Gal Syndrome and Asymptomatic Alpha-Gal Sensitization

Publication date: Available online 17 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): J. Mehlich, J. Fischer, C. Hilger, K. Swiontek, M. Morisset, F. Codreanu-Morel, M. Schiener, S. Blank, M. Ollert, U. Darsow, T. Biedermann, B. Eberlein

Abstract

Background

The alpha-gal syndrome is characterized by the presence of sIgE antibodies to alpha-gal and delayed type I allergic reaction to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal) after consumption of mammalian (red) meat products and drugs of a mammalian origin. Diagnostics currently rely on patient history, skin tests, determination of sIgE antibodies, oral food or drug challenges.

Objective

Assessing the utility of different basophil parameters (basophil reactivity and sensitivity, the ratio of the percentage of allergen-induced CD63⁺ basophils to percentage of anti-FcεRI antibody-induced CD63⁺ basophils [%CD63⁺/anti-FcεRI], the area under the dose-response curve [AUC]) as biomarkers for the clinical outcome of patients with alpha-gal syndrome compared to individuals with asymptomatic alpha-gal sensitization.

Methods

Besides routine diagnostics, a basophil activation test (Flow CAST^®) with different concentrations of alpha-gal-containing allergens (e.g., commercially available alpha-gal-carrying proteins, pork kidney extracts) was performed in 21 patients with alpha-gal syndrome, 12 alpha-gal sensitized individuals and 18 controls.

Results

Alpha-gal-containing allergens induced strong basophil activation in a dose-dependent manner in patients. Basophil reactivity at distinct allergen concentrations, the ratio %CD63+/anti-FcεRI across most allergen concentrations, the area under the curve (AUC) of dose-response curves and CD-sens with pork kidney extract were significantly higher in patients with alpha-gal syndrome compared to sensitized individuals. All parameters were negative in controls.

Conclusion

The basophil activation test should be considered as an additional diagnostic test before performing time-consuming and potentially risky oral provocation tests. The ratio %CD63⁺/anti-FcεRI for all allergens and AUC for pork kidney were the best parameters for distinguishing patients with alpha-gal syndrome from individuals with asymptomatic alpha-gal sensitization.

Clinical implications

Distinct parameters of the basophil activation test allowed a good differentiation between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization and should be determined before performing oral provocation tests.

Graphical abstract

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