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. 2022 Oct;52(10):1183-1194.
doi: 10.1111/cea.14128. Epub 2022 Apr 1.

Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma

Carlos Cardoso-Vigueros  1 , Tobias von Blumenthal  2 , Beate Rückert  2 , Arturo O Rinaldi  2 , Ge Tan  2 , Anita Dreher  3 , Urszula Radzikowska  2   3 , Günter Menz  4 , Peter Schmid-Grendelmeier  1   3 , Cezmi A Akdis  2   3 , Milena Sokolowska  2   3
Affiliations

Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma

Carlos Cardoso-Vigueros et al. Clin Exp Allergy. 2022 Oct.

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.

Keywords: asthma phenotypes; biological therapy; corticosteroids resistance; leukocyte redistribution; severe asthma; treatment asthma.

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Conflict of interest statement

CC reported grants from GSK, honoraria from AstraZeneca and GSK. PS reports honoraria from GSK, Novartis and Sanofi. CA reported research grants from Allergopharma, Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, AstraZeneca and SciBase, advisory board of Sanofi/Regeneron, GSK and Novartis, consulting fees from Novartis. MS reported research grants from Swiss National Science Foundation, Novartis and GSK and speaker's fee from AstraZeneca and a leadership in the European Academy of Allergy and Clinical Immunology: Secretary of the Board of the Basic and Clinical Immunology Section. Other authors did not report any conflict of interest.

Figures

FIGURE 1
FIGURE 1
Intravenous injection with steroids reveals two clusters of severe asthma patients
FIGURE 2
FIGURE 2
Cluster 1 and 2 patients with severe asthma differ at baseline in the frequency of eosinophils, lymphocytes and neutrophils, as well as in the magnitude of leukocyte redistribution after GC treatment
FIGURE 3
FIGURE 3
Cluster 1 and Cluster 2 patients with severe asthma differ at baseline in the frequency of CD3+ T cells, CD4+ T cells, B cells, NK cells and in the response of these populations to CS administration
FIGURE 4
FIGURE 4
Cluster 2 patients showed higher baseline total IgE levels and aeroallergen sensitization
FIGURE 5
FIGURE 5
Medical hypothesis: proposed 2‐step algorithm to identify two clusters of patients with severe asthma based on the leukocyte redistribution trial after systemic CS administration
See this image and copyright information in PMC

Comment in

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