血液 CD62Llow 炎症性嗜酸性粒细胞与哮喘的严重程度相关，美泊利单抗可降低炎症性嗜酸性粒细胞水平
2024/06/11
摘要
背景：根据 CD62L表达，嗜酸性粒细胞可以被分为具有不同表型的不同亚群。 目前尚无嗜酸性粒细胞亚型与哮喘严重程度相关性分析以及抗 IL-5 治疗对嗜酸性粒细胞亚型影响的研究。本研究探索了血液 CD62Llow 炎症性嗜酸性粒细胞 (iEos) 与重度嗜酸性粒细胞性哮喘 (SEA) 严重程度的相关性，并评估了美泊利单抗对 iEos 的影响。
方法：本研究筛选了112名患者，将其分为两组：未接受过生物治疗的患者 (n= 51) 和接受生物治疗的患者 (n= 61)。对未接受过生物治疗的患者在治疗前进行分析（A 组），并对 51 名患者中的 19 名使用美泊利单抗 100 mg 皮下注射4 周患者的治疗前后进行纵向分析（B 组）； 32 名患者因正在接受其他生物疗法被排除。通过流式细胞术(FACS)分析血液嗜酸性粒细胞亚型并与临床特征进行相关性分析。进一步通过体外实验评估了 IL-5 和美泊利单抗对 CD62L 表达的影响。
结果：在未接受生物制剂治疗的患者中，血液 CD62Llow 细胞与哮喘和鼻息肉的临床评分以及过去一年哮喘急性发作次数之间存在显著相关性。在纵向研究的患者中，CD62Llow 细胞显著减少，同时 CD62Lbright 细胞比例增加，与哮喘控制改善相关。在体外实验中，嗜酸性粒细胞上的 CD62L 表达受到 IL-5 和抗 IL-5 的调节。
结论：CD62Llow iEos 与伴有慢性鼻窦炎合并鼻息肉 (CRSwNP) 的 SEA 患者基线临床特征相关。此外，美泊利单抗可恢复 SEA 患者嗜酸性粒细胞亚型之间的健康平衡。
Blood CD62Llow inflammatory eosinophils are related to the severity of asthma and reduced by mepolizumab
Vultaggio A, Accinno M, Vivarelli E, Mecheri V, Maggiore G, Cosmi L, Parronchi P, Rossi O, Maggi E, Gallo O, Matucci A.
Allergy. 2023;78(12):3154-3165. doi:10.1111/all.15909
Abstract:
Background: Eosinophils have been divided into different subpopulations with distinct phenotypes based on CD62L expression. No data are available regarding the correlation between eosinophils subphenotypes and clinical severity of asthma, as well as the effect of anti-IL-5 therapy on these cells. The study investigates the correlation between blood CD62Llow inflammatory eosinophils (iEos) and clinical severity of severe eosinophilic asthma (SEA) and evaluates the impact of mepolizumab on iEos.
Methods: 112 patients were screened and were divided in two groups: biologicalnaive (n= 51) and biological-treated patients (n= 61). The Biological-naive patients were analyzed before treatment (Group A) and 19 out of 51 patients, were longitudinally analyzed before and after treatment with mepolizumab 100 mg s.c/4 weeks (Group B); 32 patients were excluded because they were being treated with other biological therapies. Blood eosinophils were analyzed by FACS and correlated with clinical scores. In vitro effect of IL-5 and mepolizumab on CD62L expression was assessed.
Results: A significant correlation between blood CD62Llow cells and clinical scores of asthma and nasal polyps, as well as the number of asthma exacerbations in the last year was shown in untreated patients. In longitudinally studied patients we observed a marked reduction of CD62Llow cells paralleled by an increase in the proportion of CD62Lbright cells, associated with clinical improvement of asthma control. In vitro, CD62L expression on eosinophils is modulated by IL-5 and anti-IL-5.
Conclusion: A positive correlation between CD62Llow iEos and the baseline clinical features of SEA with CRSwNP was shown. Furthermore mepolizumab restores the healthy balance among eosinophils sub-phenotypes in SEA patients.
背景：根据 CD62L表达，嗜酸性粒细胞可以被分为具有不同表型的不同亚群。 目前尚无嗜酸性粒细胞亚型与哮喘严重程度相关性分析以及抗 IL-5 治疗对嗜酸性粒细胞亚型影响的研究。本研究探索了血液 CD62Llow 炎症性嗜酸性粒细胞 (iEos) 与重度嗜酸性粒细胞性哮喘 (SEA) 严重程度的相关性，并评估了美泊利单抗对 iEos 的影响。
方法：本研究筛选了112名患者，将其分为两组：未接受过生物治疗的患者 (n= 51) 和接受生物治疗的患者 (n= 61)。对未接受过生物治疗的患者在治疗前进行分析（A 组），并对 51 名患者中的 19 名使用美泊利单抗 100 mg 皮下注射4 周患者的治疗前后进行纵向分析（B 组）； 32 名患者因正在接受其他生物疗法被排除。通过流式细胞术(FACS)分析血液嗜酸性粒细胞亚型并与临床特征进行相关性分析。进一步通过体外实验评估了 IL-5 和美泊利单抗对 CD62L 表达的影响。
结果：在未接受生物制剂治疗的患者中，血液 CD62Llow 细胞与哮喘和鼻息肉的临床评分以及过去一年哮喘急性发作次数之间存在显著相关性。在纵向研究的患者中，CD62Llow 细胞显著减少，同时 CD62Lbright 细胞比例增加，与哮喘控制改善相关。在体外实验中，嗜酸性粒细胞上的 CD62L 表达受到 IL-5 和抗 IL-5 的调节。
结论：CD62Llow iEos 与伴有慢性鼻窦炎合并鼻息肉 (CRSwNP) 的 SEA 患者基线临床特征相关。此外，美泊利单抗可恢复 SEA 患者嗜酸性粒细胞亚型之间的健康平衡。
(1四川大学华西医院呼吸与危重症医学科 高思洋1 王霁1 王刚1译)
(Allergy. 2023;78(12):3154-3165. doi:10.1111/all.15909)
(Allergy. 2023;78(12):3154-3165. doi:10.1111/all.15909)
Blood CD62Llow inflammatory eosinophils are related to the severity of asthma and reduced by mepolizumab
Vultaggio A, Accinno M, Vivarelli E, Mecheri V, Maggiore G, Cosmi L, Parronchi P, Rossi O, Maggi E, Gallo O, Matucci A.
Allergy. 2023;78(12):3154-3165. doi:10.1111/all.15909
Abstract:
Background: Eosinophils have been divided into different subpopulations with distinct phenotypes based on CD62L expression. No data are available regarding the correlation between eosinophils subphenotypes and clinical severity of asthma, as well as the effect of anti-IL-5 therapy on these cells. The study investigates the correlation between blood CD62Llow inflammatory eosinophils (iEos) and clinical severity of severe eosinophilic asthma (SEA) and evaluates the impact of mepolizumab on iEos.
Methods: 112 patients were screened and were divided in two groups: biologicalnaive (n= 51) and biological-treated patients (n= 61). The Biological-naive patients were analyzed before treatment (Group A) and 19 out of 51 patients, were longitudinally analyzed before and after treatment with mepolizumab 100 mg s.c/4 weeks (Group B); 32 patients were excluded because they were being treated with other biological therapies. Blood eosinophils were analyzed by FACS and correlated with clinical scores. In vitro effect of IL-5 and mepolizumab on CD62L expression was assessed.
Results: A significant correlation between blood CD62Llow cells and clinical scores of asthma and nasal polyps, as well as the number of asthma exacerbations in the last year was shown in untreated patients. In longitudinally studied patients we observed a marked reduction of CD62Llow cells paralleled by an increase in the proportion of CD62Lbright cells, associated with clinical improvement of asthma control. In vitro, CD62L expression on eosinophils is modulated by IL-5 and anti-IL-5.
Conclusion: A positive correlation between CD62Llow iEos and the baseline clinical features of SEA with CRSwNP was shown. Furthermore mepolizumab restores the healthy balance among eosinophils sub-phenotypes in SEA patients.
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2型生物标志物低的重度哮喘中的血液转录组特征和哮喘控制
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