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The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization

Published:August 17, 2018DOI:https://doi.org/10.1016/j.jaci.2018.06.049

      Background

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

      Objective

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

      Methods

      In addition to routine diagnostics, a basophil activation test (Flow CAST) with different concentrations of alpha-gal–containing allergens (eg, commercially available alpha-gal–carrying proteins and pork kidney extracts) was performed in 21 patients with alpha-gal syndrome, 12 alpha-gal–sensitized subjects, and 18 control subjects.

      Results

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

      Conclusion

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

      Graphical abstract

      Key words

      Abbreviations used:

      AHSG (Human alpha 2–Heremans-Schmid glycoprotein), alpha-gal (Galactose-alpha-1,3-galactose), AUC (Area under the curve), BAT (Basophil activation test), %CD63+/anti-FcεRI (Ratio of the percentage of CD63+ basophils induced by the alpha-gal–containing allergen to the percentage of CD63+ basophils after stimulation with anti-FcεRI antibody), CD-sens (Basophil allergen threshold sensitivity), EC50 (Half-maximum effective concentration or effective dose at 50% of the maximum dose response), P patients (Patients with alpha-gal syndrome, diagnosed by positive oral food challenges or presenting a very convincing medical history of systemic type I reactions of severity grades I to III after exposure to alpha-gal–containing substances), ROC (Receiver operating characteristic), sIgE (Serum specific IgE), SPT (Skin prick test), SPPT (Skin prick-to-prick test), S subjects (Sensitized subjects with sIgE to alpha-gal values of 0.10 kU/L or greater without an explicit medical history of allergic type I reactions to mammalian red meat products)
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