Treatment with Omalizumab in adults with severe allergic reduces Fc?I expression on dendritic cells and improves antiviral responses

Introduction and Aim: Severe asthma is characterised by frequent exacerbations with the majority triggered by viral infections. Treatment of severe allergic asthma with Omalizumab reduces exacerbation risk. We sought to determine how Omalizumab improved antiviral innate immune responses to influenza A (IAV) and rhinovirus (RV). Methods: We recruited 10 adults, with severe allergic asthma and 10 healthy controls. Participants were assessed at basdeline 4 and 24 weeks after treatment. Peripheral blood monocytes (PBMCs) were isolated, exposed to IAV, RV. Monocyte cell types and FceI expression was identified by flow cytometry, Response was assessed by ELISA/RNA for FceI, interferon (IFN)-a, IFN-l, IFN-g, IL-6, IL-10. Results: At base line visit subjects with severe allergic asthma compared to healthy controls demonstrated impaired IFN-α, and IFN-λ release in response to IAV (p<0.001) and RV (p=0.003). FcεI was expressed on Dendritic cells (DC) and basophils. Following 4 weeks treatment there was a marked reduction in FcεI expression on DCs associated with improved IFN-a/l responses to IAV and RV. Following 24 weeks treatment, 8/10 demonstrated reduced exacerbations. In the clinical responders DC FcεI expression remained suppressed and there was a significant increase in DC IFN-α/λ responses to IAV and a trend towards improvement to RV. Conclusion: Adults with severe allergic asthma demonstrate impaired systemic DC immune responses to IAV and RV. Treatment with Omalizumab, that results in reduced exacerbations is associated with reduced DC FcεI expression, enhanced DC IFN-α/λ responses to viruses and this effect is seen within 4 weeks treatment.