IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab

Abstract

Background: Whether IgE affects eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unclear. Moreover, our understanding of local IgE, eosinophils, and omalizumab efficacy in CRSwNP remains limited.

Objective: We investigated whether IgE acts directly on eosinophils and determined its role in omalizumab therapy.

Methods: Eosinophils and their surface receptors were detected by hematoxylin and eosin staining and flow cytometry. IgE and its receptors, eosinophil peroxidase (EPX), eosinophilic cationic protein, and CCR3 were detected by immunohistochemistry and immunofluorescence. Functional analyses were performed on blood eosinophils and polyp tissues. Logistic regression was performed to screen for risk factors. Receiver operating characteristic curve was generated to evaluate the accuracy.

Results: Both FcεRI and CD23 were expressed on eosinophils. The expression of FcεRI and CD23 on eosinophil in nasal polyp tissue was higher than in peripheral blood (both P < .001). IgE and EPX colocalized in CRSwNP. IgE directly promoted eosinophil migration by upregulating CCR3 in CRSwNP but not in healthy controls. Omalizumab and lumiliximab were found to be effective in restraining this migration, indicating CD23 was involved in IgE-induced eosinophil migration. Both IgE⁺ and EPX⁺ cells were significantly reduced after omalizumab treatment in those who experienced response (IgE⁺ cells, P = .001; EPX⁺ cells, P = .016) but not in those with no response (IgE⁺ cells, P = .060; EPX⁺ cells, P = .151). Baseline IgE⁺ cell levels were higher in those with response compared to those without response (P = .024). The baseline local IgE⁺ cell count predicted omalizumab efficacy with an accuracy of 0.811.

Conclusions: IgE directly promotes eosinophil migration, and baseline local IgE⁺ cell counts are predictive of omalizumab efficacy in CRSwNP.

Keywords: C-C motif chemokine receptor 3 (CCR3); CD23; Eosinophils; immunoglobulin E (IgE); migration; omalizumab; predictor.