血清细胞外囊泡中的 Galectin-10 反映了哮喘的病理生理学特征
2024/04/24
摘要
背景：支气管哮喘（BA）有多种表型和内型，迫切需要新的生物标志物（BMs）。
目的：我们试图从血清细胞外囊泡 (EV) 中鉴定出反映组织病理学的新型生物标记物。
方法：我们对4名健康对照组4名非嗜酸性粒细胞性哮喘（NEA）患者和4名嗜酸性粒细胞性哮喘（EA）患者的血清 EVs 进行了数据独立采集，以鉴定 BA 的新型 BMs。我们通过对61名 BA 患者和23名对照组进行数据独立采集验证，确认了 EA 特异性 BMs。为了进一步验证这些发现，我们对6名无鼻息肉的慢性鼻炎患者和 7 名有鼻息肉的慢性鼻炎患者进行了数据独立采集。
结果：我们鉴定了3032个蛋白质，其中 23 个在 EA 中表现出差异表达。Ingenuity通路分析显示，每种表型的蛋白质特征都反映了疾病特征。验证发现了5种 EA 特异性 BM，包括 半乳糖凝集素- 10 (Gal10)、嗜酸性粒细胞过氧化物酶、主要碱性蛋白、嗜酸性粒细胞衍生神经毒素和花生四烯酸 15-脂氧合酶。在诊断能力和检测气道阻塞方面，EVs 中 Gal10 的潜力优于嗜酸性粒细胞。在鼻炎患者中，从EVs和组织中分别鉴定出了1752和8413种蛋白质。在慢性鼻炎伴鼻息肉患者的EV和组织中鉴定出的11种BMs中，有5种（包括Gal10和嗜酸性粒细胞过氧化物酶）在EV和组织之间显示出显著的相关性。EVs 中 Gal10 的释放与体外和体内嗜酸性粒细胞胞外陷阱死亡有关。
结论：血清EVs中的Gal10等新型BMs反映了BA的疾病病理生理学，可能是液体活检方法的一个新靶点。
Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology
Yoshimura, H., Takeda, Y., Shirai, Y., Yamamoto, M., Nakatsubo, D., Amiya, S., Enomoto, T., Hara, R., Adachi, Y., Edahiro, R., Yaga, M., Masuhiro, K., Koba, T., Itoh-Takahashi, M., Nakayama, M., Takata, S., Hosono, Y., Obata, S., Nishide, M., Hata, A., … Kumanogoh, A.
Abstract
Background:Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes.
Objectives:We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs).
Methods:We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps.
Results:We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo.
Conclusion:Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.
背景：支气管哮喘（BA）有多种表型和内型，迫切需要新的生物标志物（BMs）。
目的：我们试图从血清细胞外囊泡 (EV) 中鉴定出反映组织病理学的新型生物标记物。
方法：我们对4名健康对照组4名非嗜酸性粒细胞性哮喘（NEA）患者和4名嗜酸性粒细胞性哮喘（EA）患者的血清 EVs 进行了数据独立采集，以鉴定 BA 的新型 BMs。我们通过对61名 BA 患者和23名对照组进行数据独立采集验证，确认了 EA 特异性 BMs。为了进一步验证这些发现，我们对6名无鼻息肉的慢性鼻炎患者和 7 名有鼻息肉的慢性鼻炎患者进行了数据独立采集。
结果：我们鉴定了3032个蛋白质，其中 23 个在 EA 中表现出差异表达。Ingenuity通路分析显示，每种表型的蛋白质特征都反映了疾病特征。验证发现了5种 EA 特异性 BM，包括 半乳糖凝集素- 10 (Gal10)、嗜酸性粒细胞过氧化物酶、主要碱性蛋白、嗜酸性粒细胞衍生神经毒素和花生四烯酸 15-脂氧合酶。在诊断能力和检测气道阻塞方面，EVs 中 Gal10 的潜力优于嗜酸性粒细胞。在鼻炎患者中，从EVs和组织中分别鉴定出了1752和8413种蛋白质。在慢性鼻炎伴鼻息肉患者的EV和组织中鉴定出的11种BMs中，有5种（包括Gal10和嗜酸性粒细胞过氧化物酶）在EV和组织之间显示出显著的相关性。EVs 中 Gal10 的释放与体外和体内嗜酸性粒细胞胞外陷阱死亡有关。
结论：血清EVs中的Gal10等新型BMs反映了BA的疾病病理生理学，可能是液体活检方法的一个新靶点。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2024 Mar 14. DOI: 10.1016/j.jaci.2023.12.030)
(J Allergy Clin Immunol. 2024 Mar 14. DOI: 10.1016/j.jaci.2023.12.030)
Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology
Yoshimura, H., Takeda, Y., Shirai, Y., Yamamoto, M., Nakatsubo, D., Amiya, S., Enomoto, T., Hara, R., Adachi, Y., Edahiro, R., Yaga, M., Masuhiro, K., Koba, T., Itoh-Takahashi, M., Nakayama, M., Takata, S., Hosono, Y., Obata, S., Nishide, M., Hata, A., … Kumanogoh, A.
Abstract
Background:Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes.
Objectives:We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs).
Methods:We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps.
Results:We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo.
Conclusion:Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.
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神经调节肽受体介导轻度哮喘患者气道2型先天性淋巴细胞的快速激活
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