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X-linked recessive ichthyosis: an impaired barrier function evokes limited gene responses before and after moisturizing treatments
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
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2012 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 167, no 3, 514-522 p.Article in journal (Refereed) Published
Abstract [en]

Background

X-linked recessive ichthyosis (XLRI) is due to deletions or inactivating mutations in the steroid sulfatase (STS) gene. This results in an accumulation of cholesterol sulphate affecting the packing of intercorneocyte lipids. XLRI is characterized by dry, scaly skin and increased skin barrier permeability; patients are often dependent on daily use of moisturizers.

Objectives

To examine the biophysical and molecular changes in the skin of patients with XLRI compared with healthy volunteers, and to analyse the effects of moisturizers on the patients' barrier function.

Methods 

Patients with XLRI (= 14) and healthy controls (= 14) were included in the study. Skin dryness score, transepidermal water loss (TEWL) and skin surface pH were monitored at baseline, and punch biopsies were obtained for mRNA expression profiles determined by oligonucleotide arrays. Measurements were repeated in the patients with XLRI after a 4-week treatment with three different moisturizers on the volar forearms. Results  Patients with XLRI showed, compared with healthy controls, increased dryness and TEWL, equal skin pH and altered expression of 27 genes. There were no signs of activation of inflammation or repair pathways. Five selected genes were significantly altered also on quantitative polymerase chain reaction analysis. Treatment with the moisturizers showed similar effects: they improved skin dryness but had no effect on TEWL, pH or expression of selected genes.

Conclusions 

Despite a dysfunctional skin barrier, the limited number of genes altered in XLRI skin suggests that no inflammatory or repair mechanisms are triggered. Treatment with moisturizers does not have any major impact on the skin barrier properties of patients with XLRI.

Place, publisher, year, edition, pages
2012. Vol. 167, no 3, 514-522 p.
National Category
Dermatology and Venereal Diseases
Identifiers
URN: urn:nbn:se:uu:diva-180402DOI: 10.1111/j.1365-2133.2012.10979.xISI: 000308130900011PubMedID: 22486194OAI: oai:DiVA.org:uu-180402DiVA: diva2:550019
Available from: 2012-09-06 Created: 2012-09-06 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Skin Barrier Function and mRNA Expression Profiles in Patients with Atopic Dermatitis, Ichthyosis Vulgaris, and X-linked Recessive Ichthyosis: Aetiopathogenic Differences and the Impact of Moisturizing Treatment
Open this publication in new window or tab >>Skin Barrier Function and mRNA Expression Profiles in Patients with Atopic Dermatitis, Ichthyosis Vulgaris, and X-linked Recessive Ichthyosis: Aetiopathogenic Differences and the Impact of Moisturizing Treatment
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Atopic dermatitis (AD), ichthyosis vulgaris (IV), and X-linked recessive ichthyosis (XLRI) are characterized by dry skin and impaired skin barrier. AD and IV are related to loss-of-function mutations in FLG (encoding filaggrin), whereas XLRI is caused by deletions or inactivating mutations in the steroid sulphatase gene (STS). Patients regularly use moisturizing creams, but little is known about the creams’ effects on the skin barrier.

The present work combines objective scorings, non-invasive techniques, and molecular analyses of skin biopsies to characterize the skin in 57 patients with AD, IV, or XLRI, and in 14 healthy controls. Patients were classified according to their FLG and STS mutation status: AD with FLG+/+ (n = 14), AD with FLG+/– (n = 14), AD/IV with FLG–/– (n = 15), and XLRI with STS– (n = 14), as well as one man with a novel point mutation. Assessments were conducted at baseline and after four weeks of treatment with three different moisturizers applied to volar forearm skin.

At baseline, dryness scoring and non-invasive assessments verified impaired skin barrier function in all patients. In patients with AD/IV, microarray analysis identified 300–3000 up- or downregulated mRNA transcripts involved in signalling pathways important for inflammation and barrier repair. The skin phenotype and number of altered transcripts were correlated with the FLG mutation status, with FLG–/– patients displaying the highest transepidermal water loss (TEWL) and the most altered transcript levels. In contrast, despite an equally dysfunctional skin barrier, only limited changes in mRNA transcripts occurred in XLRI patients. Treatment with moisturizers improved skin dryness similarly in all groups, but TEWL behaved differently: it decreased slightly in the AD/IV group and increased in the XLRI group, especially after urea treatment. Only minute effects on skin pH and mRNA expression were observed.

In conclusion, FLG mutations elicit pro-inflammatory mechanisms probably aimed at restoring barrier competence. This does not occur in patients with XLRI, presumably because STS deficiency automatically increases the barrier thickness. Moisturizing treatment improves skin dryness in patients with AD, IV, or XLRI, but does not seem to normalize the altered epidermal gene expression profile in AD/IV patients.

 

 

 

 

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 859
Keyword
atopic dermatitis, ichthyosis vulgaris, X-linked recessive ichthyosis, skin barrier function, moisturizers, transepidermal water loss, gene expression
National Category
Dermatology and Venereal Diseases
Research subject
Dermatology and Venerology
Identifiers
urn:nbn:se:uu:diva-192396 (URN)978-91-554-8583-2 (ISBN)
Public defence
2013-03-08, Rosénsalen, Ingång 95/96, Akademiska Sjukhuset, Uppsala, 09:00 (Swedish)
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Available from: 2013-02-15 Created: 2013-01-20 Last updated: 2013-04-02

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Hoppe, TorborgVahlquist, AndersBerne, BeritTörmä, Hans

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