Omalizumab response correlates with reduced IFN-γ-, IL-10- and IL-31-secreting cells in chronic spontaneous urticaria.

Abstract

The anti-IgE antibody omalizumab has been approved for the treatment of chronic spontaneous urticaria (CSU) in patients insufficiently responding to antihistamines. However, its mode of action in CSU is not clearly understood. The aim of this study was to get a better insight in the immune mechanisms involved in clinical improvement of CSU patients treated with omalizumab. Chronic spontaneous urticaria patients (n=15) were followed for 5months after initiation of omalizumab treatment. Clinical symptoms were assessed by UCT and CU-Q2 oL. Cell-bound IgE was quantified on both FcεRI- and FcεRII-expressing cell populations in peripheral blood. In addition, IgE and IgG as well as their receptors were measured on basophils, and basophil activation was assessed with different concentrations of anti-FcεRI and fMLP. Furthermore, the frequencies of different T-cell subsets secreting IL-5, IL-10, IL-31 or IFN-γ were analysed by ELISpot assay. Seven patients showed a full, five a partial and three no clinical response to omalizumab. Cell-bound IgE was reduced on FcεRI-bearing cells, but not on FcεRII-expressing cells. Likewise, the expression of FcεRI declined. Basophil activation increased upon FcεRI-stimulation while their sensitivity was not affected. Both basophil and T-cell frequencies remained unchanged. However, when comparing the individual response to omalizumab treatment with distinct T-cell subsets, a significant correlation was found between improved UCT and decreased frequencies of IL-10-, IL-31- and IFN-γ-secreting T cells. We here show that besides addressing IgE-dependent immune mechanisms, omalizumab treatment of CSU patients has effects on distinct T-cell subsets, which correlate with clinical improvement.