Clinical and translational allergy · 2025
Distinct Effects of Biological Treatments on Eosinophils and Neutrophils in Chronic Rhinosinusitis With Nasal Polyp Patients.
СтатьяНазвание и аннотация: Перевод в очереди
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Van Nevel Sharon, Zhang Nan, Xu Zhaofeng, Blauwblomme Manon, Vandewalle Elke, Holtappels Gabriele, De Ruyck Natalie, Van Nieuwerburgh Filip, Vanhee Stijn, Gevaert Philippe, Bachert Claus
Аннотация
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally characterized by tissue-infiltrating eosinophils. Various biologic treatments, targeting the inflammation, have demonstrated efficacy in reducing nasal polyp size and symptoms. However, their specific impact on granulocyte populations within polyps remains largely unclear. This study explores how different biological treatments modulate local nasal polyp inflammation by assessing changes in granulocyte presence and recruitment before and after treatment.
METHODS: Type 2-high CRSwNP patients received treatment with mepolizumab, benralizumab, omalizumab, or dupilumab. Immunohistochemistry and protein measurements were performed on their nasal polyp tissue. Bulk RNA-sequencing was conducted on pre- and post-treatment nasal samples, identifying differentially expressed genes. These results were integrated with single-cell data from CRSwNP patients.
RESULTS: Nasal polyp tissue from type 2-high patients exhibited substantial eosinophil infiltration and limited neutrophils present. All tested biologics reduced eosinophil-related proteins and genes in nasal tissue. However, our data suggest that benralizumab, mepolizumab and omalizumab could induce a concurrent upregulation of neutrophilic markers. In these patients, chemoattractant genes for neutrophils primarily originated from the epithelial cell cluster, whereas receptors for these biologics were expressed by plasma cells, dendritic cells, and mast cells.
CONCLUSION: Biological treatments effectively reduced eosinophilic inflammation in nasal polyps. However, most biologics could induce an eosinophil-to-neutrophil shift, indicating that solely targeting eosinophils may be insufficient as a treatment approach. Understanding these secondary effects on local immune pathways is critical for optimizing CRSwNP treatment strategies.
METHODS: Type 2-high CRSwNP patients received treatment with mepolizumab, benralizumab, omalizumab, or dupilumab. Immunohistochemistry and protein measurements were performed on their nasal polyp tissue. Bulk RNA-sequencing was conducted on pre- and post-treatment nasal samples, identifying differentially expressed genes. These results were integrated with single-cell data from CRSwNP patients.
RESULTS: Nasal polyp tissue from type 2-high patients exhibited substantial eosinophil infiltration and limited neutrophils present. All tested biologics reduced eosinophil-related proteins and genes in nasal tissue. However, our data suggest that benralizumab, mepolizumab and omalizumab could induce a concurrent upregulation of neutrophilic markers. In these patients, chemoattractant genes for neutrophils primarily originated from the epithelial cell cluster, whereas receptors for these biologics were expressed by plasma cells, dendritic cells, and mast cells.
CONCLUSION: Biological treatments effectively reduced eosinophilic inflammation in nasal polyps. However, most biologics could induce an eosinophil-to-neutrophil shift, indicating that solely targeting eosinophils may be insufficient as a treatment approach. Understanding these secondary effects on local immune pathways is critical for optimizing CRSwNP treatment strategies.