RT Journal Article
T1 Mepolizumab treatment alters the functional phenotype of eosinophils in severe eosinophilic asthma
A1 Miguéns Suárez, Pablo
A1 Martelo Vidal, Laura
A1 Vázquez Mera, Sara
A1 Nieto Fontarigo, Juan José
A1 Salgado Castro, Francisco Javier
A1 González Barcala, Francisco Javier
K1 Anti-IL-5 mAb
K1 Biologic
K1 Eosinophil activation
K1 Eosinophil subsets
K1 IL-5
K1 Severe asthma
AB Background: Blood eosinophil count is usually employed as a predictive and response biomarker for mepolizumab treatment. However, its decrease is not always associated with an improvement in asthma symptoms. The aim of this work is to study the effect of mepolizumab in the activation status and functional phenotype of circulating eosinophils.Methods: Samples from healthy controls (N = 15) and patients with severe eosinophilic asthma (N = 15) before and after 4, 16 and 32 weeks of mepolizumab treatment (anti-IL5 mAb; 100 mg s.c./4 weeks) were screened. Demographic, clinical, hematological and biochemical characteristics were collected. Activation and functional phenotype of peripheral blood eosinophils was analyzed by flow cytometry. sCD62L in serum was measured by ELISA. Target mRNAs were quantified by Nanostring.Results: Eosinophils from severe eosinophilic asthma patients showed a higher activation profile (CD11b, CD44 and IL-5Rα expression) compared to healthy subjects. Mepolizumab treatment reduced the number of basophils and eosinophils in peripheral blood. We also found a clear downmodulation on the surface expression (% and MFI) of CD44 and IL-3Rα on eosinophils at week 4, which was maintained through all treatment period (4–32 weeks). The functional phenotype of the remaining eosinophils was also modified with the treatment, showing a reduction of inflammatory eosinophils (iEOS; CD62Llo) percentage without affecting the balance of regulatory subpopulations (CD16dim/hi eosinophils). This was accompanied by a decrease in serum sCD62L levels. mRNA and protein levels showed similar trends for some targets (e.g., IL-5Rα) but not for others (e.g., CD62L).Conclusions: Mepolizumab treatment modifies the functional phenotype of eosinophils resulting in a lower percentage of iEOS and reduced activation status. These changes occur at an early time point (4 weeks) and are maintained throughout all treatment period.
PB Frontiers Media
YR 2025
FD 2025-11-27
LK https://hdl.handle.net/10347/46467
UL https://hdl.handle.net/10347/46467
LA eng
NO Miguéns-Suárez P, Martelo-Vidal L, Vázquez-Mera S, Blanco-Aparicio M, Calvo-Álvarez U, González-Fernández C, Mosteiro-Añón M, Corbacho-Abelaira D, Hermida-Valverde T, Calvo-Henríquez C, Nieto-Fontarigo JJ, Salgado FJ and González-Barcala FJ (2025) Mepolizumab treatment alters the functional phenotype of eosinophils in severe eosinophilic asthma. Front. Immunol. 16:1654111. doi: 10.3389/fimmu.2025.1654111
NO The author(s) declare financial support was received for the research and/or publication of this article. This work was supported by GSK (NCT04641741, GSK study id 214072) and Xunta de Galicia (ED431F 2023/15). GSK was provided the opportunity to review a preliminary version of this publication for factual accuracy, but the authors are solely responsible for final content and interpretation. The publication is part of the grant RYC2021- 032676-I financed by MCIN/AEI/10.13039/501100011033 and by the European Union NextGeneration EU/PRTR. SV and PM are recipients of a Xunta de Galicia PhD Fellowship (co-financed by European Social Fund, ESF).
DS Minerva
RD 23 may 2026