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

Background: 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. Objective: We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Ret expression and function of NP ASCs from patients with AERD and CRSwNP. Methods: 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-5Ret functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing. Results: 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-5Ret. 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. Conclusion: NP tissue ASCs from patients with AERD express higher levels of functional IL-5Ret and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin -tolerant CRSwNP. (J Allergy Clin Immunol 2024;153:527-32.)