Pediatric AD Associated with Increased β- Glucocerebrosidase Activity

Alan Irvine, PhD

A new investigation of pediatric patients with atopic dermatitis found increased β- glucocerebrosidase (GBA) activity in addition to increased glucosyl cholesterol levels.

The new data suggested an association between increased GBA activity and inflammation in disturbed lipid processing.

Atopic dermatitis has been characterized by abnormalities in lipid organization as well as immune dysregulations and an impaired skin barrier, with investigators believing that alteration in GBA activity contributes to skin barrier defects in patients with atopic dermatitis.

As such, a team of investigators led by Alan Irvine, PhD, Trinity College Dublin, Ireland, investigated GBA activity in the stratum corneum of children with atopic dermatitis before and after topical corticosteroid therapy compared with healthy controls.

The Methods

The cohort of the present study was culled from larger study of 100 infants who presented with atopic dermatitis at Children’s Health Ireland at Crumlin, Dublin.

A total of 3 subgroups were randomly selected from the original cohort, including 22 patients with atopic dermatitis and 17 healthy controls, 19 patients with atopic dermatitis and 9 healthy controls for glucosyl cholesterol, and 17 patients with atopic dermatitis and 8 healthy controls for ceramide (CER) analysis.

Disease severity of affected patients was assessed by a Scoring Atopic Dermatitis (SCORAD) score, while a sampling of the stratum corneum was collected by using circular adhesive tapes that were placed on non-lesioned forearms skin of patients and healthy controls.

A total of 8 consecutive tape strips were collected from the same skin site and placed individually in 2-mL cryovials before being stored at –80°C.

For the analysis of glucosyl cholesterol and GBA activity, the second consecutive tape from the same skin site was used, while the third tape was used to gauge CER, and the fourth and fifth tape for natural moisturizing factor (NMF) and cytokines, respectively.

Finally, lipid markers and cytokines of type 1 T helper (Th1) and Th2 immunity were assessed in healthy children and from clinically unaffected skin of children with atopic dermatitis before and after 6 weeks of therapy with topical corticosteroids.

The Findings

Investigators observed that GBA activity was significantly higher in patients with atopic dermatitis at baseline as compared to healthy controls, but decreased after 6 weeks of therapy.

The same pattern was observed regarding glucosyl cholesterol, as baseline values were higher in patients with atopic dermatitis when compared to healthy controls and decreased after therapy.

However, glucosyl cholesterol and GBA activity were still higher in patients with atopic dermatitis than healthy controls, with both correlating with transepidermal water loss and levels of multiple cytokines including IL1α and IL-18.

Overall, Irvine and colleagues believed the data convincingly demonstrated that non-lesioned skin of children with atopic dermatitis showed increased GBA activity and higher levels of glucosyl cholesterol, with the latter being strongly associated with disease severity.

“This is the first time that GlcChol was measured in atopic skin, but its function still must be clarified,” the team wrote.

The study, "Children with atopic dermatitis show increased activity of β- glucocerebrosidase and stratum corneum levels of glucosylcholesterol that are strongly related to local cytokine milieu," was published online in the British Journal of Dermatology.