415 Endotyping of adult and paediatric atopic dermatitis; is it one disease?

Abstract

The goal of this study was to show the biological heterogeneity of adult AD based on serum biomarkers and to study the heterogeneity of paediatric AD by identifying biomarker profiles in children within different age groups and compare these profiles with adult biomarker profiles, as an indication of persistence of disease. A cohort of 152 moderate to severe adult AD patients and a cohort of 240 mild to severe paediatric AD patients (aged 0-17 years) were included in this study. 143 serum analytes were measured on a multiplex immunoassay platform in both cohorts. Population heterogeneity was assessed by principal component analysis (PCA) followed by unsupervised k-means cluster analysis of the principal components. Clusters identified in the adult cohort were compared with the clusters identified in our previously described study. To investigate the differences between the age groups in the paediatric cohort, the association between the defined clusters and age groups were studied a posteriori. Secondly, the effect of age was studied by analyzing the data with a supervised cluster approach (Sparse Partial Least Squares) and compare the generated clusters with the unsupervised ones. Four distinct clusters characterised by a specific serum biomarker profile were identified in the adult AD cohort. The serum biomarker profiles of three of the four clusters were comparable with the four clusters found in our previous cohort of adult AD patients. The paediatric study is currently running and will be finished in August 2019. In this study we have repeatedly shown that adult AD is a heterogeneous disease both clinically and biologically, which emphasizes the robustness of our findings. The distinct AD patient clusters found in our studies could represent endotypes with unique biological mechanisms. The identification of endotypes enables more specific targeting of the underlying disease pathways and will contribute to more personalized medicine in the future.