Centre for Human Drug Research, Leiden, The Netherlands.
Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Exp Dermatol. 2024 Oct;33(10):e15185. doi: 10.1111/exd.15185.
Psoriasis is an inflammatory skin disease associated with an impaired skin barrier. The skin barrier function is dependent on the extracellular lipid matrix which surrounds the corneocytes in the stratum corneum. Ceramides comprise essential components of this matrix. Alterations in the stratum corneum ceramide profile have been directly linked to barrier dysfunction and might be an underlying factor of the barrier impairment in psoriasis. In this study, we investigated the ceramide profile and barrier function in psoriasis. Lesional and non-lesional skin of 26 patients and 10 healthy controls were analysed using in-depth ceramide lipidomics by liquid chromatography-mass spectrometry. Barrier function was assessed by measuring transepidermal water loss. Lesional skin showed a significant decrease in the abundance of total ceramides with significant alterations in the ceramide subclass composition compared to control and non-lesional skin. Additionally, the percentage of monounsaturated ceramides was significantly increased, and the average ceramide chain length significantly decreased in lesional skin. Altogether, this resulted in a markedly different profile compared to controls for lesional skin, but not for non-lesional skin. Importantly, the reduced barrier function in lesional psoriasis correlated to alterations in the ceramide profile, highlighting their interdependence. By assessing the parameters 2 weeks apart, we are able to highlight the reproducibility of these findings, which further affirms this connection. To conclude, we show that changes in the ceramide profile and barrier impairment are observed in, and limited to, lesional psoriatic skin. Their direct correlation provides a further mechanistic basis for the concomitantly observed impairment of barrier dysfunction.
银屑病是一种炎症性皮肤病，与皮肤屏障受损有关。皮肤屏障功能依赖于细胞外脂质基质，该基质环绕角质层中的角质细胞。神经酰胺是该基质的重要组成部分。角质层神经酰胺谱的改变与屏障功能障碍直接相关，可能是银屑病屏障损害的潜在因素。在这项研究中，我们研究了银屑病中的神经酰胺谱和屏障功能。使用液相色谱-质谱法进行深入的神经酰胺脂质组学分析，对 26 名患者和 10 名健康对照者的皮损和非皮损皮肤进行了分析。通过测量经表皮水分流失来评估屏障功能。与对照和非皮损皮肤相比，皮损皮肤中的总神经酰胺丰度显著降低，神经酰胺亚类组成也发生了显著改变。此外，皮损皮肤中的单不饱和神经酰胺百分比显著增加，平均神经酰胺链长显著缩短。与对照皮肤相比，皮损皮肤的神经酰胺谱明显不同，但非皮损皮肤则不然。重要的是，皮损银屑病中的降低的屏障功能与神经酰胺谱的改变相关，突出了它们的相互依赖性。通过评估相隔 2 周的参数，我们能够突出这些发现的可重复性，进一步证实了这种联系。总之，我们表明，在皮损银屑病皮肤中观察到神经酰胺谱的改变和屏障损伤，并且仅限于皮损银屑病皮肤。它们的直接相关性为同时观察到的屏障功能障碍提供了进一步的机制基础。
