Space (for) oddity at the skin surface: Enlarged view on the ceramide bio-signature in sebaceous and non sebaceous areas in atopic dermatitis

Derangement of ceramide levels in the skin permeability barrier (SPB) is widely demonstrated in atopic dermatitis (AD). By GCMS chemometric analysis we have observed significant deficiency of sebum-specific free fatty acids (FFAs), i.e. species with odd carbon number and terminal branching, in association to sebostasis in AD sebum. To investigate the interplay between sebum and epidermal lipids, we conducted a targeted LCMS study on the sphingolipidome of the stratum corneum (SC) in sebaceous and non sebaceous areas. The study involved 44 adult controls and 54 age and gender balanced AD patients, which included 20 with uninvolved face and 34 with involved face. SC was sampled from forehead, cheek, and non lesional arm. We profiled 111 all-classes ceramides, i.e. arising from the binding of P, S, DS, and H long chain bases (LCBs) with hydroxylated and non hydroxylated FAs, indicated as A and N, respectively. SC from facial sites presented higher levels (pmol/mg protein) of species belonging to the CerAH, CerAS and CerNS classes compared to arm, in controls and both AD subgroups. Medium-to-short and odd chained species (C≤44) were largely responsible for the discrimination between sebaceous and non-sebaceous areas. Facial sphingolipid signature was more effective than arm sphingolipidome in discriminating controls from both AD groups, being 60 and 40 ceramide species significantly different in face and arm SC, respectively. Modification of CerAH, CerAP, and CerNS level was more pronounced at sebum-rich areas than arm. Odd-chained ceramides accounted for half of the total discriminating species in all cases. These findings support a role played by the sebaceous secretion in the plasticity of the SPB. Ceramide bio-signature in sebaceous areas may empower the characterization of AD patients.