Systemic and stratum corneum biomarkers of severity in infant atopic dermatitis include markers of innate and T helper cell-related immunity and angiogenesis

BackgroundBiomarkers of atopic dermatitis (AD) are largely lacking, especially in infant AD. Those that have been examined to date have focused mostly on serum cytokines, with few on noninvasive biomarkers in the skin. ObjectivesWe aimed to explore biomarkers obtainable from noninvasive sampling of infant skin. We compared these with plasma biomarkers and structural and functional measures of the skin barrier. MethodsWe recruited 100 infants at first presentation with AD, who were treatment naive to topical or systemic anti-inflammatory therapies, and 20 healthy children. We sampled clinically unaffected skin by tape stripping the stratum corneum (SC). Multiple cytokines and chemokines and natural moisturizing factor were measured in the SC and plasma. We recorded disease severity and skin barrier function. ResultsNineteen SC and 12 plasma biomarkers showed significant differences between healthy and AD skin. Some biomarkers were common to both the SC and plasma, and others were compartment specific. Identified biomarkers of AD severity included T helper 2-skewed markers [interleukin (IL)-13, CCL17, CCL22, IL-5]; markers of innate activation (IL-18, IL-1, IL1, CXCL8) and angiogenesis (Flt-1, vascular endothelial growth factor); and others (soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, IL-16, IL-17A). ConclusionsWe identified clinically relevant biomarkers of AD, including novel markers, easily sampled and typed in infants. These markers may provide objective assessment of disease severity and suggest new therapeutic targets, or response measurement targets for AD. Future studies will be required to determine whether these biomarkers, seen in very early AD, can predict disease outcomes or comorbidities. What's already known about this topic? Atopic dermatitis is a clinically heterogeneous condition with multiple clinical manifestations and a complex pathogenesis. Systemic biomarkers of severity have been identified in adults, but are less well defined in children. Biomarkers from the skin compartment have been based on biopsies to date. What does this study add? Noninvasive sampling can detect clinically relevant biomarkers in AD skin. These biomarkers may be useful for disease stratification, and provide insights into the pathogenesis of infant AD. Innate immune activation is important in the epidermis in infantile AD. What is the translational message? Noninvasive biomarkers can yield significant insights into infantile AD. They identify innate activation, the T helper 2 pathway and angiogenesis as important pathways in this condition. Respond to this article Linked Comment: Hijnen. Br J Dermatol 2019; 180:455-456. Plain language summary available online