Atopic dermatitis (AD) is a well-studied chronic inflammatory skin disease. However, analysis of the disease's impact on the serum proteome has not been well investigated. With this study we aimed for a comprehensive characterization of the disease proteome and its change after systemic treatment. Global spectrometric profiles have been generated from 61 AD patients before (BL) and 3 months after initiation of dupilumab treatment (DPL) as well as from 30 healthy controls (HC) using LC-MS/MS technology. Endotype detection has been performed using model-based clustering. Predictability of the endotypes has been assessed using linear support vector machines. Differential abundance testing has been conducted using linear models. Proteomic profiles of patients at baseline showed considerable heterogeneity and were robustly classifiable into two endotypes BL1 and BL2. Endotype membership could be predicted with median balanced accuracy of 0.96 (LQ=0.94, UQ=0.98). Although clinically indistinguishable at baseline, the endotypes showed differences in regard to longer-term response to dupilumab therapy as measured by e.g. EASI at 18M (p=2.43E-03), IGA at 18M (p=6.19E-03) and SCORAD at 21M (p=2.15E-02). Differential abundance testing of baseline profiles with respect to HC revealed 588 and 829 proteins to be significantly altered in BL1 and BL2. Differential abundances detected for a direct comparison between BL1 and BL2 amounted to 164. The observed alterations affect proteins related to the regulation of the immune system (IL1R, IL6R, IL13RA1, TNFRSF21), the organization of the extracellular matrix (TNC, collagens, integrins) as well as the central carbon metabolism (ENOA, G6PD, TKT, TALDO). In conclusion, we report putative serum proteomic endotypes that enable accurate prediction of response to treatment of atopic dermatitis.

ESDR090 - Serum proteomic endotypes are predictive for response to treatment of atopic dermatitis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.