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.