Blood eosinophil subtype distribution following treatment with mepolizumab in patients with severe eosinophilic asthma

<bold>Introduction:</bold> Eosinophils have been divided into distinct subtypes - inflammatory-like (iEOS) and resident-like (rEOS) cells - based on CD62L expression. While it is known that mepolizumab spares residual unaltered eosinophils (Van Hulst G, et. al. Eur Respir J 2022, 59(3)), there is a lack of data about dynamic changes in blood eosinophil subtype distribution following anti-IL5 treatment. <bold>Aim:</bold> to investigate blood eosinophil subtype distribution following treatment with mepolizumab in patients with severe eosinophilic asthma (SEA). <bold>Methods:</bold> 10 free of oral steroids patients with SEA were included. Patients were treated with mepolizumab 100 mg subcutaneously/4 weeks, and eosinophil purification was performed at 0, 4, 12, and 24 weeks. Blood eosinophils were isolated by Ficoll centrifugation and magnetic separation, then subtyped using magnetic separation against CD62L. Asthma control test (ACT), FeNO, total IgE, complete blood count, and spirometry were also done. <bold>Results:</bold> At baseline (0 weeks), 72.9±4.3% of total isolated blood eosinophils were iEOS-like cells vs. 27.1±4.3% rEOS-like cells, p<0.01. Following treatment with mepolizumab blood eosinophil count consistently decreased by 85.6 - 89.3%. In addition, residual blood eosinophils shifted towards rEOS-like cells - 62.1±5.6%; 61.2±4.4%; and 63.4±4.3% of total isolated eosinophils vs. iEOS-like cells after 4, 12 and 24 weeks of treatment respectively, p<0.05. Lastly, a significant increase in ACT scores and FEV1 was noted, with no changes in FeNO and total IgE. <bold>Conclusion:</bold> Treatment with mepolizumab shifts blood eosinophil subtype distribution towards rEOS-like cells in patients with SEA.