{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sohail A"],"funding":["NIAID NIH HHS","National Institutes of Health","GlaxoSmithKline Inc"],"pagination":["527-532"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922123"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["153(2)"],"pubmed_abstract":["<h4>Background</h4>Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis.<h4>Objective</h4>We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP.<h4>Methods</h4>NP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing.<h4>Results</h4>Compared with polyp tissue from patients with CRSwNP, polyp tissue from patients with AERD contained significantly more ASCs and had increased ASC expression of IL-5Rα. ASCs from patients with AERD expressed higher protein levels of B-cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. ASCs from patients with AERD also expressed more IL5RA, IGHE, and cell cycle- and proliferation-related transcripts (CCND2, MKI67, CDC25A, and CDC25B) than did ASCs from patients with CRSwNP. Stimulation of plasma cells from patients with AERD with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from patients with CRSwNP induced few transcriptomic changes.<h4>Conclusion</h4>NP tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin-tolerant CRSwNP."],"journal":["The Journal of allergy and clinical immunology"],"pubmed_title":["Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease."],"pmcid":["PMC10922123"],"funding_grant_id":["K23 AI139352","U19 AI095219"],"pubmed_authors":["Lee SE","Lederer J","Maxfield A","Sohail A","Hacker J","Ryan T","Bhattacharyya N","Bergmark R","Buchheit KM","Laidlaw TM","Griffith A","McGill A","Jule AM","Roditi R"],"additional_accession":[]},"is_claimable":false,"name":"Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease.","description":"<h4>Background</h4>Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis.<h4>Objective</h4>We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP.<h4>Methods</h4>NP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing.<h4>Results</h4>Compared with polyp tissue from patients with CRSwNP, polyp tissue from patients with AERD contained significantly more ASCs and had increased ASC expression of IL-5Rα. ASCs from patients with AERD expressed higher protein levels of B-cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. ASCs from patients with AERD also expressed more IL5RA, IGHE, and cell cycle- and proliferation-related transcripts (CCND2, MKI67, CDC25A, and CDC25B) than did ASCs from patients with CRSwNP. Stimulation of plasma cells from patients with AERD with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from patients with CRSwNP induced few transcriptomic changes.<h4>Conclusion</h4>NP tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin-tolerant CRSwNP.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2025-04-21T23:51:51.358Z","creation":"2025-04-05T19:20:37.683Z"},"accession":"S-EPMC10922123","cross_references":{"pubmed":["37898408"],"doi":["10.1016/j.jaci.2023.10.011"]}}