Reduced Skin Barrier Function Parallels Abnormal Stratum Corneum Lipid Organization in Patients with Lamellar Ichthyosis

Abstract

Most patients with autosomal recessive lamellar ichthyosis are known to have markedly impaired skin barrier function. We hypothesize that this may be due to imperfections in the composition and fine structure of the intercellular stratum corneum lipids. The aim of the present study was to test this hypothesis. To characterize the barrier properties in three female patients with lamellar ichthyosis, the following parameters were used and compared with those of healthy volunteers: transepidermal water loss, stratum corneum lipid profiles after topical acetone/ether extraction on the flexure side of the forearm, and small-angle x-ray diffraction. The extracted lipids were separated using high performance thin-layer chromatography and quantified, and the ceramide profile was determined. Small-angle x-ray diffraction was used to obtain information on the molecular structure and organization of the intercellular lipid domains of stratum corneum using stratum corneum scales collected by scraping. Transepidermal water loss was significantly increased in all three patients. Lipid analysis showed significant differences in the relative amounts of ceramide fractions 2-3a-3b-4-5, free fatty acid-ceramide ratio, and free fatty acid-cholesterol ratio. Small-angle x-ray diffraction showed smaller repeated distances of lipid bilayers in stratum corneum samples of the patients compared with the healthy volunteers. An additional diffraction peak was found in the patients compared with the healthy volunteers, which can be ascribed to crystalline cholesterol. These data suggest that there might be a relation between the impaired barrier function and stratum corneum lipid structural and composition changes.

Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

“…These levels are comparable to those reported for other ichthyoses with a similar phenotype, such as nonbullous CIE and TGM1-negative LI (46,47).…”

“…Although a functional barrier abnormality is present in all ARCI subtypes studied to date (19,46), structural and biochemical differences between the LI and the CIE phenotypes provided initial clues about the heterogeneity within this group of ichthyoses (54,56,66). The major distinguishing feature of the LI phenotype is abnormal cornified envelope cross-linking attributable to TGM1 deficiency, resulting in attenuated cornified envelopes (19).…”

“…However, in CIE, several variable ultrastructural features were observed only in subsets of patients. These variable findings include the following: 1) an absence of electron-lucent lamellae; 2) abnormal spacing and interruptions of lamellar structures; and 3) intracellular lipid droplets and vesicular complexes, within both the SC and the SG (10,46,56,66,67). An alternative classification of the variable ultrastructural findings in ARCI is widely applied in Europe: type I is characterized by abundant lipid droplets within corneocytes; type II shows polygonal clefts within the SC; type III shows vesicular and membranous structures in the SG; and type IV is characterized by lentiform swollen areas within corneocytes and perinuclear accumulation of curved membranes in the SG (55,66).…”

Endogenous β-glucocerebrosidase activity in Abca12epidermis elevates ceramide levels after topical lipid application but does not restore barrier function

“…Because serine palmitoyltransferase initiates de novo sphingolipid synthesis by condensing serine and palmitoyl-CoA ( Fig. 1 ), use of radiolabeled serine allows for the monitoring of de novo synthesized glucosylceramide ␤ -Glucocerebrosidase assays SC samples were scraped from E18.5 embryo skins, and then tissue lysates and in vitro measurements were performed as described previously ( 20,21 ). For in situ activity, embryo whole-skin peels were preincubated with 0.54% sodium taurocholate in McIlvaine citrate-phosphate buffer pH 5.6 (taurocholate buffer) ( 21 ) in the presence or absence of 10 mM CBE for 30 min.…”

Effect of compositions in nanostructured lipid carriers (NLC) on skin hydration and occlusion

“…The organized structure of lipids is related to the barrier properties of the skin. 4,5 The skin is a viscoelastic organ. 6,7 Elastic components are made of collagen and elastic fibers; viscous parts are formed based on friction between cells and collagen bundles and other components of the dermal matrix.…”