Clin Exp Allergy. 2020;00:1–10. wileyonlinelibrary.com/journal/cea | 1 © 2020 John Wiley & Sons Ltd 1 | INTRODUCTION Severe uncontrolled asthma is a heterogeneous disease charac- terized by the persistence of the symptoms, history of exacerba- tions, and impaired lung function, despite the use of high doses of anti-asthma drugs recommended by GINA guidelines. 1 Several clinical studies have reported an association between the sensi- tization to Staphylococcus aureus enterotoxins (SEs) and severe asthma. 2-6 In particular, a recent longitudinal study has shown that SE sensitization is associated with an increased risk of developing Received: 28 March 2020 | Revised: 8 October 2020 | Accepted: 17 October 2020 DOI: 10.1111/cea.13772 ORIGINAL ARTICLE Asthma and Rhinitis Basophil activation test for Staphylococcus aureus enterotoxins in severe asthmatic patients Martina Flora 1 | Francesco Perna 2 | Salvatore Abbadessa 3 | Federica Garziano 4 | Rosalba Maffucci 1 | Mauro Maniscalco 5 | Mariano Mollica 1 | Corrado Pelaia 6 | Eugenio Tremante 7 | Marianna Maffei 7 | Cecilia Calabrese 1 1 Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy 2 Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy 3 Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy 4 Clinical Biochemistry Unit, A.O.R.N. Ospedali dei Colli, Naples, Italy 5 Pulmonary Rehabilitation Unit, ICS Maugeri SpA, IRCCS, TeleseTerme, Italy 6 Department of Health Sciences, University “Magna Graecia” of Catanzaro, Italy 7 Otolaryngology Head and Neck Surgery Unit, A.O.R.N. Ospedali dei Colli, Naples, Italy Correspondence Cecilia Calabrese, Ospedali dei Colli, via Leonardo Bianchi, 80131, Naples, Italy. Email: cecilia.calabrese@unicampania.it Abstract Background: Several studies have shown an association between severe asthma and serum immunoglobulins E (IgE) against Staphylococcus aureus enterotoxins (SEs). SEs—the prototypes being types A (SEA), B (SEB) and toxic shock syndrome toxin 1 (TSST-1)—can induce both polyclonal and specific IgE responses. Objective: The aim of the study was to evaluate the ability of SEs to induce basophil activation in severe asthmatic patients using the basophil activation test (BAT). Methods: 57 severe asthmatic patients were enrolled. BAT in response to SEA, SEB and TSST-1 was performed in all patients, while serum IgE to SEA, SEB and SEC was available in 49 patients. BAT was considered positive when CD203c+ basophils to SEs were ≥5%, and the stimulation index (SI, ratio between % of CD203c+ baso- phils to SEs and to negative control) was >2. Two threshold values (>0.1 kU/L and >0.35 kU/L, respectively) were used to assess serum SEsIgE. Results: 36.8% of severe asthmatic patients had a BAT positive for at least one SE (BAT SEs+). Serum SEsIgE >0.35 kU/L (SEs IgE+) was associated with BAT SEs posi- tivity. Among patients with negative skin prick test, 35% were BAT SEs+, 30% SEs IgE+, 55% BAT or IgE− SEs+. A negative correlation between SI of BAT to SEs and both clinical (ACT score) and functional parameters was observed, together with a positive correlation of BAT with asthma exacerbations. Conclusions: The positivity of BAT for SEs in a subgroup of severe asthmatic patients further supports the pathogenic role of Staphylococcus aureus in severe asthma. KEYWORDS basophil activation test, disability, outcome, severe asthma, Staphylococcus aureus enterotoxins