Saheb Sharif-Askari Fatemeh, Hafezi Shirin, Hachim Ibrahim, Mdkhana Bushra, Salah Al-Sheakly Baraa Khalid, Saheb Sharif-Askari Narjes, Selvakumar Balachandar, Halwani Rabih
Research Institute for Medical and Health Science, University of Sharjah, Sharjah, United Arab Emirates.
Department of pharmacy practice and pharmacotherapeutics, College of pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
ERJ Open Res. 2025 Jun 16;11(3). doi: 10.1183/23120541.00700-2024. eCollection 2025 May.
Aptamers are RNA- or DNA-based oligomers with high protein-specific binding properties that have demonstrated effectiveness in targeting various proteins and treating diseases such as cancer. However, their application in regulating chronic respiratory diseases, such as chronic rhinosinusitis, is not well established.
In this study, we used the anti-IL-4Rα aptamer (anti-IL-4Rα apt) to investigate its impact on IL-4 signalling and related T-helper 2 (Th2)-type inflammation in nasal polyp tissue. To achieve this, we treated nasal polyp tissue extracted from chronic rhinosinusitis with nasal polyps (CRSwNP) patients who had undergone polypectomy with the anti-IL-4Rα apt. Furthermore, to evaluate the effects of the anti-IL-4Rα apt on NP formation, we established an eosinophilic mouse model of CRSwNP to mimic the Th2 inflammatory pathogenesis observed in CRSwNP.
Interestingly, we observed that treatment with anti-IL-4Rα apt resulted in a significant reduction in IL-4-STAT6 signalling and Th2-mediated inflammation, as demonstrated by an ∼2-fold decrease in the levels of IL-4Rα, phosphorylated STAT6 (p-STAT6) and GATA3 in treated nasal polyp (NP) tissues compared to the untreated uncinate process (p<0.001). Notably, we observed that the administration of the anti-IL-4Rα apt effectively reduced NP formation and Th2-mediated inflammation, as shown by an ∼3-fold reduction in the percentages of IL-4Rα, p-STAT6 and GATA3 positive cells in the nasal tissues of this mouse model (p<0.001).
Given that the anti-IL-4Rα apt demonstrated comparable efficacy to dupilumab - an anti-IL-4Rα therapy proven effective for CRSwNP - this research highlights the potential therapeutic efficacy of aptamers in managing chronic inflammatory conditions such as those seen in CRSwNP.
适体是基于RNA或DNA的寡聚物，具有高蛋白特异性结合特性，已证明在靶向各种蛋白质和治疗癌症等疾病方面有效。然而，它们在调节慢性呼吸道疾病（如慢性鼻窦炎）中的应用尚未得到充分证实。
在本研究中，我们使用抗IL-4Rα适体（anti-IL-4Rα apt）来研究其对鼻息肉组织中IL-4信号传导和相关辅助性T细胞2（Th2）型炎症的影响。为此，我们用抗IL-4Rα适体处理从接受过息肉切除术的慢性鼻窦炎伴鼻息肉（CRSwNP）患者中提取的鼻息肉组织。此外，为了评估抗IL-4Rα适体对鼻息肉形成的影响，我们建立了一个嗜酸性粒细胞性CRSwNP小鼠模型，以模拟在CRSwNP中观察到的Th2炎症发病机制。
有趣的是，我们观察到用抗IL-4Rα适体处理后，IL-4-STAT6信号传导和Th2介导的炎症显著减少，与未处理的钩突相比，处理后的鼻息肉（NP）组织中IL-4Rα、磷酸化STAT6（p-STAT6）和GATA3水平降低了约2倍（p<0.001）。值得注意的是，我们观察到抗IL-4Rα适体的给药有效减少了鼻息肉形成和Th2介导的炎症，该小鼠模型鼻组织中IL-4Rα、p-STAT6和GATA3阳性细胞百分比降低了约3倍（p<0.001）。
鉴于抗IL-4Rα适体显示出与度普利尤单抗相当的疗效——一种已被证明对CRSwNP有效的抗IL-4Rα疗法——这项研究突出了适体在管理慢性炎症性疾病（如CRSwNP中所见疾病）方面的潜在治疗效果。
