Corresponding author:
Alexandra F. Santos
Address: Department of Paediatric Allergy, 2nd floor,
South Wing, St Thomas’ Hospital, SE1 7EH London, United Kingdom
Telephone number: +44 (0) 20 7188 6424
Fax number: +44 (0) 20 7403 8640
Email address: alexandra.santos@kcl.ac.uk
Word count: 5043
Abstract: The basophil activation test (BAT) is a functional
assay that measures the degree of degranulation following stimulation
with allergen or controls by flow cytometry and is directly correlated
with histamine release. From the bell-shaped curve resulting from BAT in
allergic patients, basophil reactivity (given by %CD63+ basophils) and
basophil sensitivity (given by EC50 or similar) are the main outcomes of
the test. BAT takes into account all characteristics of IgE and allergen
and thus can be more specific than sensitization tests in the diagnosis
of allergic disease. BAT reduces the need for in vivo procedures, such
as intradermal tests and allergen challenges, which can cause allergic
reactions of unpredictable severity. As it closely reflects the
patients’ phenotype, it can potentially be used to monitor the natural
resolution of food allergies and to predict and monitor clinical
response to immunomodulatory treatments, such as allergen-specific
immunotherapy and biologicals. Clinical application of BAT requires
analytical validation, clinical validation, standardization of
procedures and quality assurance to ensure reproducibility and
reliability of results. Currently, efforts are ongoing to establish a
platform that could be used by laboratories in Europe and in the USA for
certification.
Abstract word count: 190
Keywords: allergy, anaphylaxis, basophil activation test, CD63,
diagnosis, immunotherapy
Statement of contribution by each named author: A.F.S. defined
the outline of the review, wrote the first draft of the sections about
allergic reactions, immune monitoring and use in clinical trials, and
coordinated the editing of the subsequent versions of the manuscript.
O.A. wrote the first draft of the sections about the clinical
applications of the basophil activation test. H.J.H. wrote the first
draft of the sections about the basic mechanisms of basophil activation.
All authors contributed to all sections and approved the final version
of the manuscript prior to submission.
The basophil activation test (BAT) is a flow cytometry laboratory assay
which measures the expression of activation markers on the surface of
blood basophils. CD63 was discovered by Edward Knol in
19911 and, since then, BAT has progressively gained
importance in the diagnosis and monitoring of allergic diseases (Figure
1). In this review, we will cover the state-of-the-art BAT technology to
explore immune mechanisms and clinical assessment of patients with
suspected IgE-mediated allergic disease. As a functional assay performed
on live cells following stimulation with allergen, BAT can be more
specific than measuring the concentration of allergen-specific IgE.
Furthermore, as a laboratory test, BAT avoids exposure of patients to
the allergen being investigated, thus making the diagnostic process
accurate, safe and more comfortable for patients and their families.