白细胞重新分布作为严重哮喘患者对皮质类固醇抵抗的免疫生物标志物
2022/05/17
摘要
背景：早期的研究表明，白细胞的重新分布可被视为对皮质类固醇（CS）临床反应的免疫学标志物，代表了严重哮喘中一个容易测量的潜在生物标志物。
目的：本研究的目的是确定白细胞重新分布作为严重哮喘患者疾病异质性的生物标志物和作为潜在CS抵抗的生物指标的效用。
方法：我们根据142名严重哮喘患者全身CS用药前后的临床数据和外周血白细胞表型的流式细胞仪结果，开发了一种无偏见的聚类方法。
结果：根据血液中嗜酸性粒细胞、中性粒细胞和淋巴细胞的差异，以及全身CS用药前后基本T细胞、B细胞和NK细胞亚群的流式细胞仪测量，我们确定了两个严重的哮喘集群，它们在细胞频率、对CS的反应和过敏状态方面存在差异。群组1中的患者在基线时有较高的血液嗜酸性粒细胞频率，对较少的过敏原敏感，并有较好的类固醇反应性，以全身CS给药后明显的白细胞重新分布来衡量。第2组的患者是由较高的B细胞频率和对多种过敏原较强的IgE致敏状态决定的。他们还显示出较高的类固醇抵抗力，作为全身CS给药后白细胞重新分布较少的临床相关因素。
结论：基于流式细胞仪的血液中免疫细胞基本种群分析及其在全身皮质类固醇给药前后的分析，可以改善严重哮喘患者的个性化治疗方法。
Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma.
Carlos Cardoso-Vigueros, Tobias von Blumenthal, Beate Rückert, Arturo O Rinaldi, Ge Tan, Anita Dreher, Urszula Radzikowska, Günter Menz, Peter Schmid-Grendelmeier , Cezmi A Akdis, Milena Sokolowska
Abstract
BACKGROUND:Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma.
OBJECTIVE:The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance.
METHODS:We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration.
RESULTS:Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B-cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS.
CONCLUSION:The flow cytometry-based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma.
背景：早期的研究表明，白细胞的重新分布可被视为对皮质类固醇（CS）临床反应的免疫学标志物，代表了严重哮喘中一个容易测量的潜在生物标志物。
目的：本研究的目的是确定白细胞重新分布作为严重哮喘患者疾病异质性的生物标志物和作为潜在CS抵抗的生物指标的效用。
方法：我们根据142名严重哮喘患者全身CS用药前后的临床数据和外周血白细胞表型的流式细胞仪结果，开发了一种无偏见的聚类方法。
结果：根据血液中嗜酸性粒细胞、中性粒细胞和淋巴细胞的差异，以及全身CS用药前后基本T细胞、B细胞和NK细胞亚群的流式细胞仪测量，我们确定了两个严重的哮喘集群，它们在细胞频率、对CS的反应和过敏状态方面存在差异。群组1中的患者在基线时有较高的血液嗜酸性粒细胞频率，对较少的过敏原敏感，并有较好的类固醇反应性，以全身CS给药后明显的白细胞重新分布来衡量。第2组的患者是由较高的B细胞频率和对多种过敏原较强的IgE致敏状态决定的。他们还显示出较高的类固醇抵抗力，作为全身CS给药后白细胞重新分布较少的临床相关因素。
结论：基于流式细胞仪的血液中免疫细胞基本种群分析及其在全身皮质类固醇给药前后的分析，可以改善严重哮喘患者的个性化治疗方法。
(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)
(Clin Exp Allergy. 2022 Mar 19. DOI: 10.1111/cea.14128)
(Clin Exp Allergy. 2022 Mar 19. DOI: 10.1111/cea.14128)
Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma.
Carlos Cardoso-Vigueros, Tobias von Blumenthal, Beate Rückert, Arturo O Rinaldi, Ge Tan, Anita Dreher, Urszula Radzikowska, Günter Menz, Peter Schmid-Grendelmeier , Cezmi A Akdis, Milena Sokolowska
Abstract
BACKGROUND:Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma.
OBJECTIVE:The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance.
METHODS:We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration.
RESULTS:Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B-cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS.
CONCLUSION:The flow cytometry-based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma.
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