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The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization - 04/01/19

Doi : 10.1016/j.jaci.2018.06.049 
Jana Mehlich a, Jörg Fischer, MD b, Christiane Hilger, PhD c, Kyra Swiontek, MSc c, Martine Morisset, MD, PhD d, Françoise Codreanu-Morel, MD d, Maximilian Schiener e, Simon Blank, PhD e, Markus Ollert, MD c, Ulf Darsow, MD a, Tilo Biedermann, MD a, Bernadette Eberlein, MD a,
a Department of Dermatology and Allergy Biederstein, Technical University of Munich, Munich, Germany 
b Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tuebingen, Tuebingen, Germany 
c Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg 
d Immunology-Allergology Department, Luxembourg Hospital, Luxembourg-Ville, Luxembourg 
e Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, Munich, Germany 

Corresponding author: Bernadette Eberlein, MD, Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteiner Str. 29, D-80802 München, Germany.Klinik und Poliklinik für Dermatologie und Allergologie am BiedersteinTechnische Universität MünchenBiedersteiner Str. 29MünchenD-80802Germany

Abstract

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.

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Graphical abstract




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Key words : Basophil activation test, alpha-gal syndrome, galactose-alpha-1,3-galactose, red meat allergy, CD63, CCR3, basophil allergen threshold sensitivity (CD-sens), asymptomatic alpha-gal sensitization

Abbreviations used : AHSG, alpha-gal, AUC, BAT, %CD63+/anti-FcεRI, CD-sens, EC50, P patients, ROC, sIgE, SPT, SPPT, S subjects


Plan


 Supported in part by the Ministry of Higher Education and Research of Luxembourg.
 Disclosure of potential conflict of interest: J. Mehlich and B. Eberlein received methodological and technical support from the company BÜHLMANN Laboratories AG (Schönenbuch, Switzerland) and received travel support from ALK-Abelló outside the submitted work. M. Schiener received travel support from ALK-Abelló and Bencard outside the submitted work. S. Blank reports grants from Allergy Therapeutics and Bencard Allergie GmbH, is a member of the advisory board and has received personal fees from Bencard Allergie GmbH, has received personal fees from Thermo Fisher Scientific and Teomed AG, and has received travel support from ALK-Abelló outside the submitted work. M. Ollert gave advice to or received an honorarium for talks from the following companies: Siemens Healthcare, Hitachi Chemical Diagnostics, Hycor, Thermo Fisher Phadia, and Bencard outside the submitted work; he also is scientific cofounder of the biotech spinoff companies PLS-Design GmbH and Tolerogenics SarL, both outside the submitted work. U. Darsow gave advice to or received an honorarium for talks or research grant from the following companies: ALK-Abelló, Bencard, Meda, Novartis, and Sanofi-Regeneron outside the submitted work. T. Biedermann received nonfinancial support from BÜHLMANN Laboratories AG and gave advice to or got a honorarium for talks or research grant from the following companies: Alk-Abelló, Astellas, Bencard, Biogen, Celgene, Janssen, Leo, Meda, Mylan, MSD, Novartis, Phadia-Thermo Fisher, and Sanofi-Regeneron outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.


© 2018  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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