Differential responses of group 2 innate lymphoid cells and TH2 cells to benralizumab in severe asthma

BACKGROUND: Severe asthma is a heterogeneous disease with variable treatment responses to biologic therapy. Conventional biomarkers, including blood eosinophil counts and fractional exhaled nitric oxide, only partially capture response heterogeneity. OBJECTIVE: 2 cells and examined their associations with clinical outcomes after benralizumab therapy. METHODS: 2 cells was evaluated by live cell imaging of secretion activity, which enables real-time visualization of cytokine secretion from individual lymphocytes. The frequencies of IL-4-, IL-5-, and IL-13-producing cells were quantified at baseline and after 24 weeks of benralizumab treatment. Clinical responses were primarily assessed by the Asthma Control Questionnaire 5, and patients were classified as experiencing response or not. STUDY REGISTRATION: Japan Registry of Clinical Trials (jRCTs031190237). RESULTS: 2 cell frequency was associated with Asthma Control Questionnaire-defined nonresponse after adjustment for blood eosinophil counts and fractional exhaled nitric oxide. CONCLUSIONS: Single-cell functional lymphocyte profiling identifies distinct innate and adaptive type 2 responses to benralizumab and provides complementary information associated with response heterogeneity in severe asthma.