Clinical validation of the basophil activation test
An essential aspect of clinical validation of BAT is to determine its
sensitivity and specificity for clinical correlates of interest. The
sensitivity and specificity of BAT for food allergies are high, despite
showing significant differences between foods. The sensitivity of BAT
for drug allergies are lower, but still BAT can be extremely useful in
the case of life-threatening drug allergies in which patients cannot be
re-challenged or in the case of drugs for which no other tests are
available. A summary of the specificity and sensitivity can be seen onTable 3 and has been previously reviewed3,58.
Food allergy is the area of Allergology in which there is the largest
evidence about the diagnostic performance and cut-offs for tests, such
as specific IgE and skin prick testing, and in which some of the largest
studies on the clinical utility of the BAT were done. Although the SPT
and specific IgE are very sensitive and positive cut-offs have been
determined to improve their specificity, the majority of food sensitized
patients fall into an immunologically grey area, i.e. have results for
SPT and specific IgE that are detectable but below the 95% PPV cut-off.
For most foods, this immunologically grey zone is wide and in such
cases, BAT provides significant value in differentiating those with true
allergy from sensitization. Even for foods for which there are
informative allergen components, for instance Ara h 2 in the case of
peanut, BAT can clarify equivocal cases and reduce the number of
patients requiring OFC. The gold-standard for the diagnosis of food
allergy is OFC. It can lead to severe acute allergic reactions, needs to
be performed in a supervised environment with the facilities and
expertise to treat allergic reactions and anaphylaxis, should they occur
and cause significant anxiety in patients, parents and even clinical
staff. Given its strong correlation with clinical reactions, BAT offers
an important safe intermediate test before a food challenge is
considered.
OFC is often also required to confirm eligibility for treatments for
food allergy, such as OIT. For clinics that do not routinely perform OFC
before starting OIT, BAT can be used as an alternative to identify
allergic patients. BAT may also provide prognostic information about
which patients would benefit the most from this
treatment76. In a peanut OIT study, participants
entering the study with low basophil responsiveness were more likely to
achieve treatment success96. In another study, using
grass pollen SCIT, basophil sensitivity improved within three weeks of
the start of the allergen immunotherapy (AIT) and correlated with
clinical outcomes after three and four years based on in vivo allergen
challenge45.
The success of the BAT is influenced by patient selection, allergens
used and criteria for cut-off values60. There are also
practical issues to consider when incorporating BAT as part of routine
diagnostic work up. For instance, although BAT to peanut showed overall
best diagnostic accuracy compared to all other tests
available40, it is easier to perform skin prick test
or specific IgE and therefore these tests can be used as first line. BAT
should be performed as a second-line test in patients with equivocal
outcome following clinical history and IgE sensitization
tests57, before referring patients for OFC. This
proposed approach reduced the number of OFC by 67% in a previous study
of peanut allergy40. To circumvent the major
limitations of BAT, which are the need for fresh blood and the 10-15%
non-responders, the mast cell activation test (MAT) may be used to
complement the BAT97.