Is basophil activation test (BAT) really useful for allergy diagnosis?

Dear Editor, both the paper by Pereira Santos et al and the Editorial on the latest issue of this Journal, stressed on the essential, fairly irreplaceable role of basophil activation test (BAT) in allergy diagnosis (1,2). Certainly, BAT is a cell-based test and in this sense it should give fundamental insights about the role of these circulating leukocytes in hypersensitivity reactions, chronic allergy and anaphylaxis (3). However, as many other analytical assays, even BAT has its Achille’s heel. Although a great deal of efforts have been attempted in order to improve the diagnostic potential of BAT, principally regarding its flow cytometry (FC) approach (4,5), operators are still using CD63% as the main tuner of the analytical decision if the activated basophils in BAT are signalling an allergic response. CD63% is an analytical algorhytm that raised some criticism and concern principally because of its relationship with an arbitrary threshold, closely dependent on the resting, non activated state of basophils, used as a negative reference control (6). Tracing a landmark of the resting, full activable basophil in a BAT is particularly difficult and attempts were suggested to address this cumbersome issue in BAT interpretation (7,8). In few words, it is practically impossible to set basophil activation on a standard resting population, because of the many reasons related to pre-analytical handling, frequency of releaser or non releaser subjects within the population, intrinsic variability due to CD63 vesicle endowment. The paper of Pereira Santos evaluated single asthmatic patients treated with omalizumab, and raised another fundamental issue in the correct use of BAT in allergy. Xolair Omalizumab is able to reduce both serum IgEs and FcεRs on basophils and dendritic cells (DCs), therefore, according to the Authors, a CD63-based BAT should probe the effect of omalizumab on basophil reactivity, following the anti-Cε3-IgE MoAbs treatment (1). However, the same Authors addressed the critical issue that BAT does not match completely the effect of omalizumab on a IgE-mediated response. The intrinsic variability in the allergic response performed by basophils, particularly addressed in the Editorial (2), might hinder the presumptive IgE/CD63 linear relationship, as expected if considering the close relationship between allergic response and CD63 membrane up-regulation. Yet, BAT is evaluated through the behaviour of a marker that does not depend exclusively on the membrane FcεRI/IgE complex expression Corresponding author Salvatore Chirumbolo University Laboratory of Medical Research (LURM) Unit of Geriatric Medicine, Room 41 Department of Medicine University of Verona, Italy Policlinico GB Rossi Piazzale L.A. Scuro 10, 37134 Verona, Italy Phone: +39 045 8128 456 E-mail: [email protected] Department of Medicine, Unit of Geriatry, University of Verona, Italy Is basophil activation test (BAT) really useful for allergy diagnosis? S. cHiruMBolo Vol 48, n 3, 107-109, 2016