Introduction: Benralizumab is an anti-interleukin-5 receptor ? monoclonal antibody with anti-eosinophilic activity. A particular mechanism of action of this drug is determined by its afucosylated constant fragment (Fc) that binds Fc?RIIIa receptors on the membrane of natural killer (NK) cells. After this interaction, NK cells activate ADCC through release of proapoptotic proteins, leading to apoptosis of eosinophils. 

Methods: We analyzed changes in NK cell phenotypes in Severe asthmatic (SA) patients, before and after six months of benralizumab. We also compared SA patients with  mild and moderate asthmatic patients (M/M) and healthy controls (HC). Multiparametric flow cytometry of NK cell subsets comprising the expression of CD57, NKG2C, NKG2A and KIR were performed. Proliferation assay was performed at baseline and during follow up of therapy.

Results: At baseline, SA patients showed higher percentages of immature NK when compared with HC. We demonstrate for the first time the in vivo proliferative capacity of these cells and their activation status after benralizumab administration through the analysis of CD137 on NK cells. NK cell phenotypes shifted towards CD56dimCD16br mature NK cells with contemporary expression of CD57 and NKG2C as markers of terminally differentiated NK cells. A correlation between the activation state of NK cells and clinical improvement, assessed by lung function tests and steroid-sparing was reported.

Conclusions: Together these data contribute to our understanding of the mechanisms of action of benralizumab in the resolution of inflammation in SA patients.