113 New IgE+ B cell subsets identified as a potential therapeutic target for atopic dermatitis

Purpose of the study: Patients with atopic dermatitis (AD) have increased plasmablasts (PBs) and memory B cells (MBs) expressing the membrane form of immunoglobulin E (mIgE) in peripheral blood. However, the detailed dysregulation of the mIgE+ B cell subsets and their roles in AD severity have not yet been explored. Methods: We investigated mIgE-expressing B cell subsets, other than MB and PB, and quantify various mIgE-expressing B cell subsets in peripheral blood mononuclear cell (PBMC) samples from 54 patients with AD and 10 healthy controls. IgE+ PB, MB, and a potentially new subset of IgE+ B cells were defined using flow cytometry and analyzed by t-distributed stochastic neighbor embedding (t-SNE). The functional role of IgE+ B subsets in AD severity was demonstrated by anti-CεmX antibody treatment in 20 moderate-to-severe AD patients. Results: Significant increases in IgD+/IgE+ B cell frequencies were observed in patients with AD compared with healthy controls, and the numbers of IgE+ PBs, IgE+ MBs, and IgD+/IgE+ B cells were positively correlated with AD severity. The frequencies of these subsets were reduced in AD patients following treatment with anti-CεmX antibody, resulting in decreased Eczema Area and Severity Index (EASI) scores in 20 patients with moderate to severe AD. Conclusions: These results demonstrate the clinical relevance of mIgE-expressing B cell populations, which might serve as potential therapeutic targets for AD treatment.