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.