Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease

Abstract

BackgroundChronic 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 cyclooxygenase-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody secreting cells (ASCs), plasma cells (PCs) and plasmablasts, in their polyp tissue, and nasal polyp IgE levels correlate with disease severity and recurrence of nasal polyposis. ObjectiveWe sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of nasal polyp ASCs from patients with AERD and CRSwNP. MethodsNasal polyp tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. Nasal polyp cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with/without IL-5 and analyzed by bulk RNA-sequencing. ResultsAERD polyp tissue contained significantly more ASCs and had increased ASC expression of IL-5Rα compared to CRSwNP. AERD ASCs expressed higher protein levels of B cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. AERD ASCs also expressed more IL5RA, IGHE, and cell cycle and proliferation-related transcripts (CCND2, MKI67, CDC25A and CDC25B) compared to CRSwNP. Stimulation of AERD PCs with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from CRSwNP induced few transcriptomic changes. ConclusionNasal polyp tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation compared to those from aspirin-tolerant CRSwNP patients.