Omalizumab dampens type 2 inflammation in a group of long‐term treated asthma patients and detaches IgE from FcεRI.

Even if omalizumab is broadly used in the treatment of severe, allergic asthma, the immunological effects in long‐term treated patients have not been fully elucidated. To this aim, a cohort of 15 allergic asthmatic patients treated with omalizumab for at least three years was compared with 12 allergic asthma patients treated with standard therapy. Omalizumab treated asthmatic patients showed lower frequencies of circulating plasmacytoid DCs, and lower CD154 expression on CD4 T‐helper cells than the control group. Moreover, basophils and DCs from omalizumab‐treated patients had lower surface expression of IgE compared to the control group. In a longitudinal evaluation of two patients that started omalizumab treatment, we show that FcεRI free of IgE were evident on basophils just after four weeks of drug administration. Finally, in vitro experiments with basophils obtained from healthy donors confirm that omalizumab is able to detach IgE from high affinity IgE receptors. Collectively these data indicate that long‐term omalizumab treatment dampens type 2 inflammation acting on different cell types that play a pivotal role in the pathogenesis of allergic asthma. Moreover, we have identified a further mechanism of action of omalizumab, such as the ability to detach IgE from its receptor. In order to define the immunological effects of the anti‐IgE mAb omalizumab, a group severe allergic asthma patients treated with omalizumab (OTP), was compared with a group of allergic asthma patients treated with standard therapy (STP). We found that omalizumab dampens type 2 inflammation in OTP. Moreover, beyond the well‐known ability of Omalizumab to bind to circulating IgE and prevent their interactions with FcεRI, we showed that omalizumab dissociate prebound IgE from its receptor on basophils. Both these mechanisms participate to the reduction of FcεRI bound IgE and FcεRI downregulation. [ABSTRACT FROM AUTHOR]