June 2024
Subsets of sputum eosinophils in asthma exacerbations
Article: Activated sputum eosinophils associated with exacerbations in children on mepolizumab
Wilson GE, Knight J, Liu Q, et al
J Allergy Clin Immunol. 2024 March
Reviewed by Jakub Novosad, MD, PhD, Institute of Clinical Immunology and Allergy, University Hospital, Hradec Kralove, Czech Republic
Despite extensive research, the mutual relationship between asthma and eosinophils is a complex and multifaceted topic that has yet to be fully understood. The current understanding of eosinophil biology suggests the existence of different functional subsets, each associated with distinct cytokine production and phenotype. Read more
This concept was first observed in the murine model of asthma by Abdala-Valencia in 2016 (Allergy 2016) and later confirmed in human asthma patients by Mesnil (J Clin Invest 2016). The model of regulatory (rEos) and inflammatory (iEos) eosinophils, with different expression of CD62L (CD62hi in rEos / CD62low in iEos), was proposed. This approach has been further explored in asthma patients treated with mepolizumab by Vultaggio (Allergy 2023). In the reviewed paper, Wilson et al. cross-sectionally analyzed sputum eosinophils in severe asthma children patients from a MUPPITS-2 study (n=53) (Jackson, The Lancet 2022), treated either by an ad on mepolizumab (n=22) or placebo (n=31) for 12 months. Induced sputum cells were analyzed using mass cytometry (CyTOF).
The authors confirmed decreased sputum eosinophils in mepolizumab-treated patients (P=0.04). They also assessed a relative abundance of sputum eosinophils concerning a history of exacerbations (no exacerbation vs ≥1 exacerbation) and treatment arm. The authors observed no difference in the placebo arm; however, in mepolizumab-treated patients, the absence of exacerbations associated with lower relative counts of eosinophils (P=0.08). Moreover, clustering analysis identified three subpopulations of sputum eosinophils based on CD62L expression (CD62Llow, CD62Lint and CD62Lhi). CD62Lint and CD62Lhi eosinophils exhibited significantly elevated activation markers and eosinophil peroxidase expression, respectively and were more abundant in mepolizumab-treated patients with exacerbations. The authors suggest that these eosinophil subpopulations may contribute to asthma exacerbations despite mepolizumab treatment. The study's strengths include its well-defined patient subpopulations, thorough cytological analysis of induced sputum and multidimensional immune profiling using CyTOF analysis. The weakness is the relatively low study sample size and its cross-sectional design. The study raises new questions regarding the role of eosinophil subsets in asthma and its exacerbation pathogenesis. Surface CD62L expression is a promising way to differentiate between distinct subpopulations. However, the results are controversial. The elevated activation status of CD62Lhi eosinophils seems contradictory to previous findings (Johansson, Frontiers in Medicine 2017), necessitating further research.
Jakub Novosad, MD, PhD, is a clinical immunologist and allergologist at the Institute of Clinical Immunology and Allergy in the University Hospital in Hradec Kralove in the Czech Republic. He finished his PhD on the immunobiology of intracellular parasitism. He currently focuses on clinical and laboratory research on immunobiology and biomarkers of eosinophilic asthma, and he is particularly interested in the clinical outcomes of biological treatment. He is a member of the National Centre for Severe Asthma in the Czech Republic, the European Academy for Allergology and Clinical Immunology (EAACI), the International Eosinophil Society (IES), the Website / Social Media Committee, and the Website Content Subcommittee.