Biosignatures of defective sebaceous gland activity in sebum-rich and sebum-poor skin areas in adult atopic dermatitis

Atopic dermatitis (AD) is a composite disease presenting disruption of the skin permeability barrier (SPB) in the stratum corneum (SC). Recent evidence supports derangement of the sebaceous gland (SG) activity in the AD pathomechanisms. The objective of this study was to delineate profiles of both sebaceous and epidermal lipids and of aminoacids from SG-rich (SGR) and SG-poor (SGP) areas in AD. Both sebum and SC were sampled from SGR areas, while SC was sampled also from SGP areas in 54 adult patients with AD, consisting of 34 and 20 subjects, respectively with and without clinical involvement of face, and in 44 age and sex-matched controls. Skin biophysics were assessed in all sampling sites. Disruption of the SBP was found to be associated with dysregulated lipidome. Abundance of sapienate and lignocerate, representing, respectively, sebum and the SC type lipids, were decreased in sebum and SC from both SGR and SGP areas. Analogously, squalene was significantly diminished in AD, regardless the site. Extent of lipid derangement in SGR areas was correlated with the AD severity. The abundance of aminoacids in the SC from SGR areas was altered more than that determined in SGP areas. Several gender-related differences were found in both controls and AD subgroups. In conclusion, the SG activity was differently compromised in adult females and males with AD, in both SGR and SGP areas. In AD, alterations in the aminoacidome profiles were apparent in the SGR areas. Lipid signatures in association with aminoacidome and skin physical properties may serve the definition of phenotype clusters that associate with AD severity and gender.Sebum is unevenly distributed on the skin surface. Sebum is more abundant on the upper trunk and on the face due to the higher number of sebaceous glands (SGs) in these areas. In principle, the epidermal permeability barrier in the stratum corneum (SC) is uniformly distributed across the body areas, with some exceptions. Although, both sebum and the permeability barrier are lipid rich compartments, their respective composition is extremely specific. Evidence is emerging that the lipid composition of the permeability barrier is different in SG-rich (SGR) and SG-poor (SGP) areas. Atopic dermatitis (AD) is characterized by disruption of the skin permeability barrier and deranged composition of epidermal lipids. Recent data demonstrate dysregulated sebum lipidome in AD. We aimed at determining key elements of the epidermal barrier, that is, lipids and natural moisturizing factors (NMFs), in both SGR and SGP areas in the population consisting of healthy controls and AD patients presenting or not the involvement of SGR areas, that is, the face. In all the study participants, TEWL and corneometry were assessed on the SGP and SGR areas. Sampling of SC was performed by tape stripping in both SGR and SGP areas, while sebum was sampled with absorbing patches only from the SGR areas. Site-specific features of the skin biophysics were observed in the three subgroups. Chemometric differences based on skin surface lipidomics and NMFs, which include aminoacids, from both SGR and SGP sites, allowed for different levels of discriminations. Multivariate approaches (ASCA) supported distinction of skin conditions and identification of biomarkers associated with severity and involvement of SGR areas.image