What can BAT tell us about allergic reactions?
Acute immediate allergic reactions and anaphylaxis result from the effect of mediators released by basophils and mast cells following exposure to the allergen. Blood basophils are more readily available in peripheral blood than tissue mast cells are and thus constitute an accessible relevant sample to study immediate allergic reactions and anaphylaxis. The BAT has shown to reflect the allergic status of patients sensitized to food, inhalant and insect venom allergens in different studies, with the basophils of allergic subjects typically showing a dose-dependent increase in the %CD63+ basophils or in the mean fluorescence intensity of CD203c 57,58. Such studies have led to a growing force into applying BAT to the diagnosis of IgE-mediated allergic disease, given its very high specificity with retained high sensitivity compared to IgE sensitization tests. In a peanut allergy study40, which was recently validated further59, the specificity of BAT to peanut ranged between 96 and 100%. Such high specificity strongly supports its use to confirm the diagnosis of food allergy and dispense patients from risky and stressful exposure to the allergen during challenges60. In patients with allergic asthma, CD-sens was correlated with allergen dose used in bronchial challenge causing a 20% drop in forced expiratory volume in 1s (PD20). This correlation was mostly due to patients with low AHR and was not seen in patients reacting with high AHR, which further suggests that this correlation is allergen-specific and that BAT reflects the allergic component in the bronchial responsiveness36. In venom allergy, BAT can add clinical value to IgE testing and can be particularly useful in cases of undetectable IgE sensitization or double sensitization to both wasp and bee venom61. BAT may also be valuable in replacing sting challenges to guide when to stop immunotherapy62.
BAT can also be useful to recognise more detailed aspects of allergic patients’ phenotype. For instance, patients with different phenotypes of milk and egg allergy have shown different profiles of CD63 upregulation following allergen stimulation with children tolerating baked milk/egg while reacting to fresh milk/whole egg showing an intermediate degree of basophil activation between children who were allergic to all forms of milk and children who had outgrown their milk/egg allergy63,64. A greater proportion of activated basophils has been associated with increasing severity of allergic reactions and basophil sensitivity with the threshold dose at which patients reacted during challenges to peanut33,59,65-68. This is another example of how BAT can be used to define more subtle characteristics of the allergic response beyond the dichotomic classification of allergic versus non-allergic.
Apart from identifying patients’ allergic status at a given time-point, BAT may be a useful tool to monitor natural changes in allergic status over time or with immunomodulatory treatments. Various studies have documented a decrease in basophil reactivity and sensitivity following allergen specific immunotherapy to food, respiratory and insect venom allergens42,45,69-71. In food allergy, a decrease in basophil reactivity during treatment has been observed to the culprit allergen and a bystander allergen as well as IgE-mediated (but not non-IgE-mediated) positive controls suggesting changes intrinsic to the basophil. These changes, which are typical of basophil anergy, accompany clinical desensitization to the allergen, as measured by the increase in threshold of reactivity while on treatment72. The decrease in basophil reactivity can be more notorious in oral compared to sublingual immunotherapy to foods, mirroring the difference in efficacy of OIT compared with SLIT in terms of the dose of allergen tolerated during treatment73. The reduction in basophil reactivity can be transient, which is similar to the clinical effect of oral immunotherapy in some patients following discontinuation of treatment73, hence a good test to monitor relapse of the allergy.