Elevated MS4A2 and IgE interaction in nasal polyps contributing to poor postoperative prognosis in patients with eosinophilic chronic rhinosinusitis

Background: Chronic rhinosinusitis (CRS) is a persistent inflammatory disease of various endotypes, including eosinophilic CRS (eCRS), which is characterized by marked eosinophilic infiltration and high refractory rates despite treatment. Recent findings suggest the interaction between local IgE and mast cells in nasal polyps (NPs) is key to eCRS pathogenesis; however, the details remain unclear. This study investigated the involvement of MS4A2, a component of the IgE receptor, in the pathogenesis of refractory eCRS. Methods: NP tissue samples were collected from 47 patients with eCRS who underwent sinus surgery and classified into refractory and nonrefractory groups based on postoperative outcomes. Quantitative PCR was used to analyze the mRNA expression of IgE receptor components (MS4A2, FCER1A, and FCER1G) and cell-specific markers (CLC, TPSAB1, and GPR56) in NP tissues. Immunofluorescence staining was used to confirm MS4A2 expression and colocalization with tryptase, ProMBP1, and IgE. ROC analysis was conducted to assess MS4A2 mRNA levels as a predictor of refractory eCRS. Results: MS4A2 mRNA expression was significantly elevated in the refractory group, whereas FCER1A and FCER1G mRNA expression levels showed no significant differences. Immunofluorescence revealed an increased number of MS4A2-positive cells, particularly those colocalized with tryptase-positive mast cells, in the refractory group. Cells coexpressing MS4A2 and IgE were more prevalent in this group. ROC analysis indicated that MS4A2 mRNA expression can predict prognosis with high specificity. Conclusions: Our findings suggest the significance of the interaction between MS4A2-expressing mast cells and local IgE in the pathogenesis of refractory eCRS, highlighting MS4A2 as a potential therapeutic target. (c) 2025 Japanese Society of Allergology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).