Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma
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 util...
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| Published in: | Clinical and experimental allergy Vol. 52; no. 10; pp. 1183 - 1194 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Wiley Subscription Services, Inc
01-10-2022
John Wiley and Sons Inc |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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.
Intravenous challenge with corticosteroids identified two clusters of patients with severe asthma, who had different leukocyte redistribution as analysed by the complete blood count and flow cytometry. Unbiased clinical phenotyping after clustering revealed that Cluster 1 and 2 patients varied slightly at baseline in clinical characteristics and in the need for systemic corticosteroids. LR might potentially serve as a biomarker of corticosteroid sensitivity to identify the biological reserve of the immune system. FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; ICS, inhaled corticosteroids; LR, leucocyte redistribution; OCS, oral corticosteroids. Created with www.biorender.com. |
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| Bibliography: | Funding Information This study was supported by the research grants from the GSK (to CC, MS and CA) and Novartis (to CA) and Swiss National Science Foundation (SNFS) (to MS). Carlos Cardoso‐Vigueros and Tobias von Blumenthal are co‐first authors, both contributed equally. |
| ISSN: | 0954-7894 1365-2222 |
| DOI: | 10.1111/cea.14128 |