The effects of Benralizumab on blood basophils in severe asthmatic patients: preliminary results

Benralizumab, a monoclonal antibody anti IL-5 receptor alpha, induces an almost complete depletion of eosinophils and a marked reduction of basophils in the blood of severe eosinophilic asthmatic patients. The mechanism underlying the different depletion rate is not clear. Previous studies suggested the existence of two basophil populations, one IL-3-elicited degranulating after IgE-crosslinking, the other, TSLP-elicited, responding more to other stimuli. The aim of the study, partially funded by AstraZeneca, was to characterize, by flow cytometry, blood basophils before and after six months of therapy with benralizumab. Blood samples were collected from 10 severe eosinophilic asthmatics, before and after six months of therapy with Benralizumab, and from 10 healthy subjects at the same timing. Basophils, identified as CRTH2+, CD203c+ and CD3- cells, were analyzed to evaluate FcεRI, IL-3R, IL-5R and TSLP-R expression. At baseline, severe asthmatics compared with healthy subjects showed a significant higher number of blood basophils and of basophils expressing FCƐRI, IL3R and IL-5R (p<0.05) and TSLPR (p<0.01). In severe asthmatic patients, benralizumab determined a significant reduction of the number of blood basophils and of basophils expressing FCƐRI and IL3R (p<0.01), IL-5R (p<0.05), without any significant effect on TSLPR+ basophils. After 6 months, the number of blood basophils and of FCƐRI+, IL3R+ and IL5R+ basophils was significantly lower in asthmatics in comparison with healthy subjects (p<0.05), while the number of TSLPR+ basophils was significantly higher (p<0.05). This study suggest the existence of distinct subsets of basophils showing a different response to Benralizumab.