Applications of basophil activation test in paediatric allergic diseases

Abstract

Basophilic granulocytes, containing and releasing histamine after a specific allergy stimulation, are directly involved in IgE-mediated allergic reactions. CD63 is a transmembrane protein of secretory lysosomes of basophils and its upregulation is related with the release of histamine to the extracellular space during IgE-mediated allergic reactions. Basophil activation test (BAT) measures the activation of circulating basophils upon the in vitro stimulation of living blood cells with specific allergens. Such a test is particularly safe and reproducible and has recently emerged as a new promising diagnostic tool for allergic diseases. BAT can be used to diagnose food allergy and represents a promising alternative to oral food challenge tests, especially in children as it is less invasive, safer, and cheaper than the gold standard tests. As a biomarker of tolerance and reactivity, it is also useful to monitor natural resolution and clinical response to immune-modulatory treatments. Regarding drug allergies, BAT is even the only possible applicable diagnostic tool for allergy reactions to some drugs, because of the lack of alternative test, or given that those commonly used are unreliable, or equivocal. Additionally, BAT allows to screen patients with more active urticarial and identify Hymenoptera-allergic patients with negative venom-specific immunoglobulin (Ig)E. In respiratory allergic diseases, BAT can facilitate the diagnosis of local allergic rhinitis and evaluate basophil allergen sensitivity in allergic asthma. Although IgE-sensitization in allergic asthma is usually demonstrated by skin prick test and specific IgE, those tests do not predict the clinical allergy contribution to asthma pathogenesis. To date, the potential of BAT in the diagnostic work-up of allergic diseases is well established, but a better standardization of its use is needed. This narrative review summarizes the state-of-the-art BAT technology and applications in pediatric allergic diseases, focusing on immune-related mechanisms and the BAT real clinical utility.

Keywords: Allergic disease; Basophil activation test; Pediatrics; Spontaneous chronic urticaria; Venom allergy.

Fig. 1

CD63 and CD203c basophil activation mechanisms. CD63 appears to be involved in cell membrane re-organization and exosome formation. Histamine released into the extracellular space inversely affects its expression. This supports the role of CD63 in IgE-mediated allergies. Thus, the allergen activation of blood basophils can be measured by histamine release or CD63 upregulation. CD63 is expressed in anaphylactic degranulation through regulated exocytosis after allergen-mediated mast cell and basophil activation, unlike histamine release in piecemeal and anaphylactic degranulation. CD203c is often measured with CD63 and appears to be co-expressed. Since CD63 and CD203c upregulation may not always correlate with total histamine release, it has been suggested that these 2 markers follow different basophil activation pathways, with CD63 reflecting anaphylactic degranulation and CD203c piecemeal degranulation

Fig. 2

Basophil Activation Test applications.