Eosinophils from healthy children (1-3 years) and adults express high levels of prostaglandin D2 receptor 2 (DP2)

Background: Eosinophils (eos) are key inflammatory cells in asthma and they are known to carry the Prostaglandin D2 receptor 2 (DP2). DP2 receptor antagonists are currently being developed for asthma and they induce a reduction of lung eos. It is assumed that DP2+ eos are key cells for the mode of action of DP2 antagonists. Aims: In this study, the expression of the DP2 receptor on peripheral blood eos and additional inflammatory cells in children (1 to 3 years) and adults (≥18 to 65 years) was analyzed to support the treatment rationale for DP2 receptor antagonists in children with asthma. Methods: Twenty healthy adults (≥18 – 65 years) and 23 healthy children (1 to 3 years) were enrolled. The frequency (%) and expression of the DP2 receptor on peripheral blood eos (primary endpoint), basophils, CD3+, CD4+, and CD8+ T cells was analyzed by a validated flow cytometry assay. Results: The frequency of DP2+ eos was high (> 98%) and there was no difference between children and adults. The geometric mean (90% CI) DP2 mean fluorescence intensity (MFI) on eos was 12 % lower in children than adults (2235 [2096-2383] versus 2549 [2389-2719]). The frequency of DP2+ basophils was > 80 % in both age groups and the geometric mean MFI was 702 (635-777) in children and 902 (815-998) in adults. The percentage of DP2+ T cell subsets tended to be lower in children while the DP2 MFI of T cell subsets was comparable in children and adults. Conclusions: The observed high frequency of DP2+ eos and the high mean expression of the DP2 receptor on eos confirm target expression in children and support the treatment rationale for DP2 receptor antagonists in children with asthma.