A Functional Cell Model using Basophil Activation Test to Study Molecular Mechanisms and Biomarkers of Response to Omalizumab Treatment in Patients with Asthma
Patients with severe asthma may benefit from targeted biological therapies. However, personalized therapy in children and adolescents with asthma, based on individual susceptibility to molecular mechanisms addressed by different biologicals is underdeveloped. Here we established a functional in vitro model to study the differential responses of asthma patients to omalizumab (an IgE targeting biological) therapy. White blood cells isolated from asthmatic children and adolescents were pre-treated with omalizumab. Next, basophil activation and degradation were used to assess the in vitro patient's response to omalizumab after exposure to patient-specific allergens. In parallel, basophils-specific whole RNA sequencing was used to screen for differentially expressed genes associated with in vitro response to omalizumab. The results of the screen were first confirmed in an independent cohort of patients and finally compared to the clinically relevant data. The in vitro basophil activation + degradation test may be used to study the differential response to omalizumab in patients. The differentially expressed genes in the basophils of the better vs. the poor / non-responders are predominantly associated with defense against viruses and apoptosis. The low RSAD2 expression correlates with poor response to omalizumab in vitro and with high FeNO levels (an indicator of lung inflammation) in the omalizumab-treated juvenile asthmatics. We describe an in vitro test to study the differential response to omalizumab in patients. RSAD2 may be a biomarker for response to omalizumab in asthma. Overall design: White blood cells isolated from asthmatic children and adolescents were pre-treated with omalizumab. Next, basophil activation and degradation were used to assess the in vitro patient's response to omalizumab after exposure to patient-specific allergens. In parallel, basophils-specific whole RNA sequencing was used to screen for differentially expressed genes associated with in vitro response to omalizumab.