Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Osaka 573-1010, Japan.
Allergy Center, Kansai Medical University Hospital, Osaka 573-1010, Japan.
Cells. 2023 Nov 30;12(23):2746. doi: 10.3390/cells12232746.
Eosinophilic airway inflammation, complicated by bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), is difficult to treat. The disease may become refractory when eosinophilic mucin associated with eosinophil peroxidase (EPX) and autoantibodies fills in the paranasal sinus and small airway. This study investigated the functional role of an anti-EPX antibody in eosinophilic mucin of ECRS in eosinophilic airway inflammation. Eosinophilic mucin was obtained from patients with ECRS. The effects of the anti-EPX antibody on dsDNA release from eosinophils and eosinophilic mucin decomposition were evaluated. Immunofluorescence or enzyme-linked immunosorbent assays were performed to detect the anti-EPX antibody and its supernatant and serum levels in eosinophilic mucin, respectively. The serum levels of the anti-EPX antibody were positively correlated with sinus computed tomography score and fractionated exhaled nitrogen oxide. Patients with refractory ECRS had higher serum levels of the anti-EPX antibody than those without. However, dupilumab treatment decreased the serum levels of the anti-EPX antibody. Immunoglobulins (Igs) in the immunoprecipitate of mucin supernatants enhanced dsDNA release from eosinophils, whereas the neutralization of Igs against EPX stopped dsDNA release. Furthermore, EPX antibody neutralization accelerated mucin decomposition and restored corticosteroid sensitivity. Taken together, the anti-EPX antibody may be involved in the formulation of eosinophilic mucin and be used as a clinical marker and therapeutic target for intractable eosinophilic airway inflammation.
嗜酸性气道炎症，并发支气管哮喘和嗜酸性慢性鼻-鼻窦炎（ECRS），治疗困难。当与嗜酸性过氧化物酶（EPX）和自身抗体相关的嗜酸性黏蛋白填充鼻窦和小气道时，疾病可能变得难治。本研究探讨了抗 EPX 抗体在 ECRS 嗜酸性黏蛋白中对嗜酸性气道炎症的功能作用。从 ECRS 患者中获得嗜酸性黏蛋白。评估抗 EPX 抗体对嗜酸性粒细胞和嗜酸性黏蛋白分解中 dsDNA 释放的影响。进行免疫荧光或酶联免疫吸附试验分别检测抗 EPX 抗体及其上清液和血清在嗜酸性黏蛋白中的水平。抗 EPX 抗体的血清水平与鼻窦计算机断层扫描评分和呼出氮氧化物分数呈正相关。难治性 ECRS 患者的抗 EPX 抗体血清水平高于非难治性患者。然而，度普利尤单抗治疗降低了抗 EPX 抗体的血清水平。黏蛋白上清液免疫沉淀中的免疫球蛋白（Igs）增强了嗜酸性粒细胞中 dsDNA 的释放，而针对 EPX 的 Igs 中和则阻止了 dsDNA 的释放。此外，EPX 抗体中和加速了黏蛋白的分解并恢复了皮质类固醇的敏感性。综上所述，抗 EPX 抗体可能参与了嗜酸性黏蛋白的形成，并可作为难治性嗜酸性气道炎症的临床标志物和治疗靶点。
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