The stratum corneum is the outermost layer of the skin, and acts as the primary barrier against penetration of pathogens, allergens and other exogenous substances into the lower layers of the skin.... Show moreThe stratum corneum is the outermost layer of the skin, and acts as the primary barrier against penetration of pathogens, allergens and other exogenous substances into the lower layers of the skin. Crucial for a proper barrier function are the lipids in the stratum corneum, mainly consisting of ceramides, free fatty acids, and cholesterol. These lipids are highly ordered stacked layers. In atopic eczema the skin barrier is impaired, but the exact role of the lipids is still uncertain. This thesis describes the importance of a proper composition and ordering of the stratum corneum lipids and their role in eczematous patients (atopic eczema and Netherton disease). The results demonstrate that patients suffering from a impaired skin barrier also show different lipid profile. In particular the carbon chain length of the lipids is notably reduced in these eczematous patients. Consequently, the stratum corneum lipids show a less ordered lipid arangement. This is the first time that a strong correlation is observed between the lipid composition, the lipid organization, and the skin barrier function. These studies therefore provide new targets for possible drug therapy of eczematous patients. Show less
The skin barrier function strongly relies on the outermost layer of the skin, the stratum corneum (SC), which consists of dead corneocytes embedded in a highly organized extracellular lipid matrix.... Show moreThe skin barrier function strongly relies on the outermost layer of the skin, the stratum corneum (SC), which consists of dead corneocytes embedded in a highly organized extracellular lipid matrix. The lipids are thought to play a crucial role in the skin barrier function. This lipid matrix consists mainly of ceramides, cholesterol and free fatty acids in an approximately equimolar ratio. Atopic eczema (AE) is a chronic relapsing inflammatory skin disease that is characterized by dryness, erythema and pruritus. AE patients have a decreased skin barrier function as monitored with transepidermal water loss. The main objective of this thesis is to determine the SC lipid composition, lipid organization and lipid/protein ratio in AE patients and control subjects and to determine how these changes are associated with the impaired skin barrier function and disease severity of AE patients. The studies demonstrate that there is an altered lipid composition and lipid/protein ratio in non-lesional as well as lesional SC of AE patients. The changes in lipid composition result in an altered lipid organization that is associated with an impaired skin barrier function in AE patients Show less
