307 Looking at vitiligo from the skin barrier point of view

Abstract

Vitiligo (VTG) is increasingly regarded as affecting the entire skin. Recently, keratinocytes have been indicated as key players in VTG being able to produce pro-inflammatory mediators involved in the immune response. Moreover, alterations in stratum corneum (SC) thickness as well as in the expression of genes participating in keratinocyte differentiation and cornification, have been observed in VTG lesional skin. To evaluate possible abnormalities of the skin barrier in non-lesional VTG skin, SC was collected from the forearm of 50 healthy subjects (HS) and 57 VTG patients. SC lipid signature was obtained by a lipidomic approach combining GC-MS and LC-MS profiles of the different lipid classes such as cholesterol (CH) and cholesterol sulfate (CHS), free fatty acids (FFAs), and ceramides (CERs). Heatmaps were employed to display the individual profiles as well as the VTG and HS mediated data. Score and loadings plots generated by ASCA analysis were utilized to evaluate significant differences in SC lipid composition. The data obtained demonstrated a higher content of FFAs in VTG in comparison to HS. Moreover, the FFAs relative composition highlighted the increase in the unsaturated fraction and the decrease of C26:0, a fatty acid with Ultra Long Chain length (ULC). VTG showed a general content reduction of CERs statistically significant for CER[NP], CER[AP], CER[AS], and CER[NDS] subclasses. Furthermore, we observed a relevant different distribution of fatty acids contained in CERs with ULC fatty acids significantly reduced in VTG patients. CH and CHS amounts resulted higher in VTG compared with HS. Overall, the data revealed remarkable differences in VTG SC lipid composition as demonstrated by the PCA plot, which allowed to separate HS from VTG. The altered ratio between CERs, FFAs, CH, and CHS may represent an index of the impairment to develop a fully-competent skin barrier in VTG, thus creating a local pro-inflammatory milieu potentially able to trigger the immune response.