The Quantification of Extracellular Trap Cell Death-Derived Products as Diagnostic Biomarkers for Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Eosinophilic Otitis Media
The Quantification of Extracellular Trap Cell Death-Derived Products as Diagnostic Biomarkers for Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Eosinophilic Otitis Media
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DOI：
10.1097/mao.0000000000003431
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发表时间：
2021-11
影响因子：
2.1
通讯作者：
S. Morita;Y. Nakamaru;Atsushi Fukuda;Keishi Fujiwara;Masanobu Suzuki;Kimiko Hoshino;A. Honma;A. Homma
中科院分区：
文献类型：
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作者：
S. Morita;Y. Nakamaru;Atsushi Fukuda;Keishi Fujiwara;Masanobu Suzuki;Kimiko Hoshino;A. Honma;A. Homma
目的：本研究旨在量化中耳液中游离脱氧核糖核酸（DNA）、瓜氨酸化组蛋白H3 (citl -H3)-DNA复合物和髓过氧化物酶(MPO)-DNA复合物作为细胞外陷阱细胞死亡（ETosis）衍生产物，并鉴定抗中性粒细胞细胞质抗体（ANCA）相关血管炎（OMAAV）与嗜酸性中耳炎（EOM）的诊断性生物标志物。研究设计：前瞻性研究。单位：三级转诊中心。患者：OMAAV患者符合纳入本分析的条件。EOM患者作为对照进行检查。干预：所有样本均取自OMAAV或EOM患者的中耳液。在显微镜下用1毫升结核菌素注射器用24或26号针从中耳经鼓膜的前-下部分抽吸液体样本。主要观察指标：采用酶联免疫吸附法测定液样中游离DNA、cit-H3-DNA复合物和MPO-DNA复合物的水平。结果：无论采样时的血清ANCA状态如何，OMAAV患者的MPO-DNA复合物水平明显高于EOM患者（p < 0.001和p < 0.001）。同时，OMAAV和EOM患者的游离DNA值和cit-H3-DNA复合物值无显著差异。结论：本研究结果提示，无论血清ANCA状态如何，中耳炎液中MPO-DNA复合物的检测和定量可用于鉴别OMAAV，特别是在嗜酸性肉芽肿病合并多血管炎的病例中。应该注意的是，液体样品中的无细胞DNA和cit-H3-DNA复合物有可能来自死细胞，而不是经历ettosis的中性粒细胞。
Objective: This study aimed to quantify the cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex as extracellular trap cell death (ETosis)-derived products in the middle ear fluid, and to identify diagnostic biomarkers for the discrimination of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) from eosinophilic otitis media (EOM). Study Design: Prospective study. Setting: Tertiary referral center. Patients: OMAAV patients were eligible for inclusion in this analysis. Patients with EOM were examined as controls. Intervention: All samples were obtained from the middle ear fluid in patients with OMAAV or EOM. The fluid samples were aspirated from the middle ear through the anterior-inferior portion of the tympanic membrane using a 1-ml tuberculin syringe with a 24- or 26-gauge needle under a microscope. Main Outcome Measures: The levels of cell-free DNA, cit-H3-DNA complex and MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay. Results: Patients with OMAAV showed significantly higher levels of MPO-DNA complex compared to patients with EOM, regardless of the serum ANCA status at the time of sampling (p < 0.001 and p < 0.001, respectively). Meanwhile, there were no significant differences in the values of cell-free DNA or cit-H3-DNA complex between the OMAAV and EOM patients. Conclusion: The findings of this study suggest that the detection and quantification of MPO-DNA complex in the otitis media fluid can be utilized to discriminate OMAAV, especially in cases of eosinophilic granulomatosis with polyangiitis, from EOM regardless of the serum ANCA status. It should be noted that it is possible for cell-free DNA and cit-H3-DNA complex in fluid samples to be derived from dead cells other than neutrophils that undergo ETosis.