Sohail Aaqib, Hacker Jonathan, Ryan Tessa, McGill Alanna, Bergmark Regan, Bhattacharyya Neil, Lee Stella E, Maxfield Alice, Roditi Rachel, Julé Amélie M, Griffith Alec, Lederer James, Laidlaw Tanya M, Buchheit Kathleen M
Department of Medicine, Harvard Medical School, the Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass.
Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass.
J Allergy Clin Immunol. 2024 Feb;153(2):527-532. doi: 10.1016/j.jaci.2023.10.011. Epub 2023 Oct 28.
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.
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.
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.
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.
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.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）会导致鼻塞和嗅觉功能障碍。阿司匹林加重性呼吸系统疾病（AERD）是CRSwNP、哮喘以及对COX-1抑制剂的呼吸道反应三联征。AERD患者鼻内白细胞介素-5（IL-5）水平升高，其息肉组织中抗体分泌细胞（ASC）数量众多，包括浆细胞和成浆细胞；此外，其鼻息肉（NP）免疫球蛋白E（IgE）水平与疾病严重程度及鼻息肉复发相关。
我们试图探究AERD患者与CRSwNP患者NP-ASC的转录组图谱、激活标志物以及IL-5Rα表达和功能的差异。
采集AERD患者和CRSwNP患者的NP组织，并消化成单细胞悬液。通过质谱流式细胞术分析NP细胞的蛋白表达。对于IL-5Rα功能研究，纯化浆细胞并在体外进行有或无IL-5培养，然后通过大量RNA测序进行分析。
与CRSwNP患者的息肉组织相比，AERD患者的息肉组织含有显著更多的ASC，且ASC中IL-5Rα的表达增加。AERD患者的ASC表达更高水平的B细胞激活和调节标志物（CD40、CD19、CD32和CD38）以及增殖标志物Ki-67。与CRSwNP患者的ASC相比，AERD患者的ASC还表达更多的IL5RA、IGHE以及细胞周期和增殖相关转录本（CCND2、MKI67、CDC25A和CDC25B）。用IL-5刺激AERD患者的浆细胞可诱导关键细胞周期基因（CCND2和PTP4A3），而用IL-5刺激CRSwNP患者的ASC则诱导很少的转录组变化。
与阿司匹林耐受的CRSwNP患者的ASC相比，AERD患者的NP组织ASC表达更高水平的功能性IL-5Rα以及与细胞周期和增殖相关的标志物。
