Background: The cause of severe nasal polyposis in aspirin-exacerbated respiratory disease (AERD) is unknown. Elevated antibody levels have been associated with disease severity in nasal polyps, but upstream drivers of local antibody production in nasal polyps are undetermined.
Objective: We sought to identify upstream drivers and phenotypic properties of local antibody-expressing cells in nasal polyps from subjects with AERD.
Methods: Sinus tissue was obtained from subjects with AERD, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps, and controls without CRS. Tissue antibody levels were quantified via ELISA and immunohistochemistry and were correlated with disease severity. Antibody-expressing cells were profiled with single-cell RNA sequencing, flow cytometry, and immunofluorescence, with IL-5Rα function determined through IL-5 stimulation and subsequent RNA sequencing and quantitative PCR.
Results: Tissue IgE and IgG4 levels were elevated in AERD compared with in controls (P < .01 for IgE and P < .001 for IgG4 vs CRSwNP). Subjects with AERD whose nasal polyps recurred rapidly had higher IgE levels than did subjects with AERD, with slower regrowth (P = .005). Single-cell RNA sequencing revealed increased IL5RA, IGHG4, and IGHE in antibody-expressing cells from patients with AERD compared with antibody-expressing cells from patients with CRSwNP. There were more IL-5Rα plasma cells in the polyp tissue from those with AERD than in polyp tissue from those with CRSwNP (P = .026). IL-5 stimulation of plasma cells in vitro induced changes in a distinct set of transcripts.
Conclusions: Our study identifies an increase in antibody-expressing cells in AERD defined by transcript enrichment of IL5RA and IGHG4 or IGHE, with confirmed surface expression of IL-5Rα and functional IL-5 signaling. Tissue IgE and IgG4 levels are elevated in AERD, and higher IgE levels are associated with faster nasal polyp regrowth. Our findings suggest a role for IL-5Rα antibody-expressing cells in facilitating local antibody production and severe nasal polyps in AERD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282948 | PMC |
| http://dx.doi.org/10.1016/j.jaci.2020.02.035 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comparing Efficacy of Steroid Irrigation + Steroid-eluting Sinus Stent Versus Steroid Irrigation Alone for Maintaining Frontal Sinus Patency After Sinus Surgery: A Randomized Controlled Trial.
Int Forum Allergy Rhinol
January 2025
Department of Otolaryngology, Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, USA.
Background: Steroid rinses and steroid-eluting stents are both options for preventing postoperative stenosis after frontal sinus surgery. This study aimed to assess whether steroid-eluting stents offer added benefit over steroid rinses alone in postoperative healing and long-term frontal sinus patency.
Methods: A randomized controlled trial enrolled patients with CRS with nasal polyps (CRSwNP) who underwent surgery for bilateral and equal frontal sinusitis after failing prior medical therapy.
Machine learning of endoscopy images to identify, classify, and segment sinonasal masses.
Int Forum Allergy Rhinol
January 2025
Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, USA.
Background: We developed and assessed the performance of a machine learning model (MLM) to identify, classify, and segment sinonasal masses based on endoscopic appearance.
Methods: A convolutional neural network-based model was constructed from nasal endoscopy images from patients evaluated at an otolaryngology center between 2013 and 2024. Images were classified into four groups: normal endoscopy, nasal polyps, benign, and malignant tumors.
Tissue Eosinophils Threshold and its Association with Adult-Onset Asthma in Chronic Rhinosinusitis.
Int Forum Allergy Rhinol
January 2025
Center of Excellence in Otolaryngology-Head & Neck Surgery, Rajavithi Hospital, Bangkok, Thailand.
Introduction: Tissue eosinophil counts (TEC) might serve as a biomarker linking chronic rhinosinusitis (CRS) and the presence of adult-onset asthma. This study aimed to determine if TEC in sinus mucosa/polyps in CRS patients is an independent indicator of asthma and to identify its optimal cut-off point.
Methods: This cross-sectional study was conducted on primary CRS patients scheduled for surgery.
Oral and intranasal aspirin desensitisation for non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease.
Cochrane Database Syst Rev
January 2025
Department of Otorhinolaryngology, Amsterdam University Medical Centre, Amsterdam, Netherlands.
Background: NSAID-exacerbated respiratory disease (N-ERD) is a hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen, accompanied by chronic rhinosinusitis (with or without nasal polyps) or asthma. The prevalence of hypersensitivity to NSAIDs is estimated to be 2%. The first line of treatment is the avoidance of NSAIDs.
View Article and Find Full Text PDFIntegrated Proteomics and Machine Learning Approach Reveals PYCR1 as a Novel Biomarker to Predict Prognosis of Sinonasal Squamous Cell Carcinoma.
Int J Mol Sci
December 2024
Department of Microbiology, Faculty of Medicine, Khon Kaen University, Mueang Khon Kaen, Khon Kaen 40002, Thailand.
Sinonasal squamous cell carcinoma (SNSCC) is a rare tumor with a high 5-year mortality rate. However, proteomic technologies have not yet been utilized to identify SNSCC-associated proteins, which could be used as biomarkers. In this study, we aimed to discover a biomarker to predict SNSCC patients using proteomic analysis integrated with machine learning models.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!