Flow-based basophil activation test in immediate drug hypersensitivity. An EAACI task force position paper

Diagnosing immediate drug hypersensitivity reactions (IDHRs) can pose a significant challenge and there is an urgent need for safe and reliable tests. Evidence has emerged that the basophil activation test (BAT), an in vitro assay that mirrors the in vivo response, can be a complementary test for many drugs. In this position paper, members of Task Force (TF) “Basophil activation test in the evaluation of Drug Hypersensitivity Reactions” from the European Academy of Allergy and Clinical Immunology (EAACI) present the data from a survey about the use and utility of BAT in IDHRs in Europe. The survey results indicate that there is a great interest for using BAT especially for diagnosing IDHRs. However, there are still main needs, mainly in the standardization of the protocols. Subsequently consensus-based recommendations were formulated for: (i) Technical aspects of BAT in IDHRs including type of sample, management of drugs, flow cytometry protocols, interpretation of the results; and (ii) Drug-specific aspects that should be taken into account when performing BAT in relation to betalactams, neuromuscular blocking agents, fluoroquinolones, chlorhexidine, opioids, radio contrast media, chemotherapeutics, biological agents, nonsteroidal anti-inflammatory drugs, COVID vaccine, and excipients. Moreover, aspects in the evaluation of pediatric population have also been considered. All this indicates that BAT offers the clinician and laboratory a complementary tool for a safe diagnostic for IDHRs, although its place in the diagnostic algorithm depends on the drug class and patient population (phenotype, geography, and age). The standardization of BAT is important for generalizing this method beyond the individual laboratory.Funding for open access charge: Universidad de Málaga/CBUA. The authors would like to thank EAACI for their financial support in the development of this Task Force Position Paper

Basophil activation test is a complementary tool in the diagnosis of immediate reactions to platinum salts and taxanes

Background Delabelling pathways offer confirmatory diagnosis and can prevent unnecessary second-line therapies or drug desensitization procedures after chemotherapeutic hypersensitivity reactions (CHT-HSRs). However, these pathways rely on risky in vivo tests. Data on whether in vitro tests could be helpful are scarce. We assessed the role of basophil activation test (BAT) in the diagnosis of HSRs to platin salts (PSs) and taxanes (TXs) in a well-defined population featuring varied endophenotypes and severities of HSRs. Methods We conducted a 3-year-long multicentric, prospective study with 121 suspected-immediate CHT-HSR patients. The allergy workup included clinical history (initial reaction based on Type I, cytokine release syndrome, and mixed phenotype's symptoms and if unable to fit in any of these, as “indeterminate”), skin testing (ST), and drug provocation testing (DPT), provided risk assessment was favorable. Final diagnosis classified patients as “hypersensitive,” “non-hypersensitive,” or “inconclusive.” We performed BAT using CD63 and CD203c as activation markers in patients and controls. Patients underwent DPT regardless of BAT results to prevent bias. Results ST positivity significantly correlated with skin involvement, Type I phenotype, cancer recurrence, and lifetime exposures before reactions. DPTs were negative in all indeterminate phenotype patients (p = .02) and those considered low-risk, whereas they were negative in 62% moderate-risk patients. 55% were confirmed as hypersensitive (mainly Type I reactions, p < .0001), 24% as non-hypersensitive (mainly TXs and indeterminate phenotypes), and 21% as inconclusive. BAT showed 79% sensitivity in Type I IgE-mediated reactions to PSs with a high correlation to ST.Funding for open access charge: Universidad de Málaga / CBUA. This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Ministry of Economy and Competitiveness (MINECO), grants co-founded by Fondo Europeo de Desarrollo Regional—FEDER for the Thematic Networks and Co-operative Research Centres: PI22/01119; PI18/00095; RETICS ARADYAL RD16/0006/0001, RICORS REI (RD21/0002/0008); Biobank network RD09/0076/00112; Biobank platform PT13/0010/0006; Andalusian Regional Ministry of Economy and Knowledge (grants PI-0076-2019). G.B. is a clinical investigator (B-0007-2022), research contract by Andalusian Regional Ministry Health. A.A. thanks Senior Postdoctoral Contract (RH-0099-2020) from Andalusian Regional Ministry of Health (co-funded by European Social Fund [ESF]: “Andalucía se mueve con Europa”) and “Nicolas Monardes” research contract by Andalusian Regional Ministry Health (C1-0007-2023). CLM holds a P-FIS contract (FI23/00027) by ISCIII. SCS holds a predoctoral contract by Andalusian Regional Goverment (PREDOC_01545). CM holds a “Nicolas Monardes” research contract by Andalusian Regional Ministry Health (RC-0004-2021)