Plasmacytoid Dendritic Cells Display Surface but Not Membrane-Bound IgE Across a Broad Range of Total Serum IgE Levels

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Introduction: Plasmacytoid dendritic cells (pDC) are unique antigen-presenting cells that may be implicated in allergic disease because they bind IgE on their surface and modulate important Th1/Th2 cytokine responses. The authors previously discovered that IgE is not readily removed from pDCs using omalizumab to the same extent observed for basophils, suggesting that a portion of the IgE on pDCs may be membrane bound. Methods: A cross-sectional study was performed and recruited adult volunteers from Johns Hopkins Asthma & Allergy Clinic, Baltimore, Maryland, USA, between 2022–2023. Individuals with varying levels of serum IgE were selected, and those on subcutaneous immunotherapy or biologic therapy were excluded. Basophils and pDCs were isolated using established protocols. In order to isolate peripheral blood mononuclear cells, blood was also drawn from consenting donors with a wide range in total serum IgE levels. B cells and pDCs were identified by flow cytometry by gating on CD19/CD27 and blood dendritic cell antigen 2/CD123, respectively. Quilizumab, a mouse anti-human monoclonal IgG1 antibody with specificity only for membrane-bound IgE and surrogate for omalizumab, was used to detect this molecule in both cell types. Results: When used in vitro at 1.5 mg/mL, omalizumab removed ~80–90% of the IgE expressed by basophils. In contrast, IgE expression decreased only 30–40% on similarly treated pDCs. There was no significant difference in the number of pDCs staining for membrane-bound IgE between the isotype control and quilizumab (P=0.125, 0.165). However, the proportion CD19+27+ B cells staining for quilizumab compared to other PBMC was 54:1 (P=0.015). Conclusion: While pDCs express significant levels of surface-bound IgE, there is no appreciable amount of membrane-bound IgE noted. The reason for omalizumab’s poor ability to remove pDC-bound IgE compared to its effectiveness at removing circulating IgE remains unknown.