engleski

Children with atopic dermatitis show increased activity of β‐glucocerebrosidase and stratum corneum levels of glucosylcholesterol that are strongly related to the local cytokine milieu

Background Atopic dermatitis (AD) is characterized by immune dysregulations and an impaired skin barrier, including abnormalities in lipid organization. In the stratum corneum (SC), b-glucocerebrosidase (GBA) mediates transformation of glucosylceramide (GlcCER) into ceramide (CER) and cholesterol into glucosylcholesterol (GlcChol). Alteration in GBA activity might contribute to skin barrier defects in AD. Objectives To investigate GBA activity in the SC of children with AD before and after topical corticosteroid therapy and to compare it with healthy controls ; to determine SC levels of GlcCER- and CER-containing hydroxysphingosine base (GlcCER[H] and CER[H], respectively) and GlcChol ; and to relate them to disease severity, skin barrier function and the local cytokine milieu. Methods Lipid markers and cytokines of innate, T helper 1 and T helper 2 immunity were determined in SC collected from healthy children and from clinically unaffected skin of children with AD, before and after 6 weeks of therapy with topical corticosteroids. AD severity was assessed by Scoring Atopic Dermatitis and skin barrier function by transepidermal water loss (TEWL). Results Baseline GBA activity and GlcChol levels were increased in children with AD but declined after therapy. CER[H] levels and the CER[H] to GlcCER[H] ratio were increased in AD. GBA activity and GlcChol correlated with TEWL and levels of multiple cytokines, especially interleukin-1a and interleukin-18. GlcChol was strongly associated with disease severity. Conclusions We show increased GBA activity and levels of GlcChol in AD. Our data suggest an important role of inflammation in disturbed lipid processing. GBA activity or GlcChol might be useful biomarkers in the monitoring of therapeutic responses in AD.

ceramides, GBA, stratum corneum, atopic dermatitis

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