Non-Releasers in the Basophil Activation Test: A Roadmap for the Correct Reporting and Interpretation

Flow cytometric analysis of activated basophils, known as the basophil activation test (BAT), is a tool available for the diagnosis of IgE-mediated allergic reactions. Despite its reported clinical utility, around 10%-20% of tested subjects fall into the category of basophil non-releasers, meaning that their basophils fail to degranulate upon IgE-mediated stimulation in vitro. Several factors causing this non-releaser status have been identified, but we currently lack a unified nomenclature to define such inconclusive BAT results and the practical steps to minimize such outcomes. In accordance with the STAndards for the Reporting of Diagnostic accuracy studies (STARD) statement, non-releasers must be reported and considered in the calculation of clinical BAT performance metrics, as failure to do so significantly limits the broader implementation of BAT in routine practice. This review provides an overview of intrinsic and extrinsic factors responsible for the basophil non-releaser phenotype in BAT. Furthermore, it proposes a standardized nomenclature for consistently reporting and integrating inconclusive BAT results in the diagnostic performance metrics and suggests diagnostic algorithms to facilitate their interpretation in clinical practice.