Dataset Information

Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity.

ABSTRACT:

Background

Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity.

Methods

The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population.

Results

The levels of PCA, UCA and HIS correlated with FLG genotype. Furthermore, these levels were higher in the CTRL when compared to AD patients with no FLG mutations. Multiple regression analysis showed that NMF levels were independently associated with FLG genotype and severity of disease.

Conclusion

Decreased NMF is a global feature of moderate-to-severe AD; within AD, FLG genotype is the major determinant of NMF, with disease severity as a secondary modifier. NMF components are reliably determined by a noninvasive and relatively inexpensive tape stripping technique.

SUBMITTER: Kezic S

PROVIDER: S-EPMC3586662 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Publications

Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity.

Kezic S S O'Regan G M GM Yau N N Sandilands A A Chen H H Campbell L E LE Kroboth K K Watson R R Rowland M M McLean W H Irwin WH Irvine A D AD

Allergy 20110125 7

<h4>Background</h4>Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of ...[more]

PMID: 21261659

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Project description:Importance:Skin microbiome correlates with disease severity for lesional and nonlesional skin, indicating a global influence of atopic dermatitis (AD). A relation between skin microbiome and filaggrin gene (FLG) mutations proposes a possible association between skin microbiome and host genetics. Objectives:To assess skin and nasal microbiome diversity and composition in patients with AD and compare with healthy controls, and to investigate the microbiome in relation to disease severity and FLG mutations in patients with AD. Design, Setting, and Participants:An observational case-control study of 45 adult healthy controls and 56 adult patients with AD was carried out from January 2015 to June 2015 in a tertiary referral center, Department of Dermatology, Bispebjerg Hospital, Denmark. Exposures:Bacterial swabs were taken from patients with AD (lesional skin, nonlesional skin, and anterior nares) and from healthy controls (nonlesional skin and anterior nares). Eczema severity was assessed and FLG mutations noted. Bacterial DNA was extracted from swabs, and V3-V4 16S rDNA regions amplified with PCR. Samples were analyzed at Statens Serum Institut September 2015 to September 2016. Bioinformatics analyses of the microbiome were analyzed using R statistical software (version 3.3.1, R Foundation Inc). Main Outcomes and Measures:Skin microbiomes were investigated using next-generation sequencing targeting 16S ribosomal RNA. Results:Microbiome alpha diversity was lower in patients with AD compared with healthy controls in nonlesional skin (effect size, 0.710; 95% CI, 0.27-1.15; P?=?.002), lesional skin (effect size, 0.728; 95% CI, 0.35-1.33; P?=?.001), and nose (effect size, 1.111; 95% CI, 0.48-0.94; P?<?.001). Alpha diversity was inversely correlated with disease severity for lesional (effect size, 0.530; 95% CI, 0.23-1.64; P?=?.02) and nonlesional skin (effect size, 0.451; 95% CI, 0.04-2.44; P?=?.04) in patients with AD. Microbiome composition in AD nonlesional skin was linked to FLG mutations. Conclusions and Relevance:An altered microbiome composition in patients with AD in nonlesional skin, lesional skin, as well as nose, suggests a global influence of AD. Microbiome composition in AD nonlesional skin is associated with FLG mutations, proposing a possible association between the skin microbiome and host genetics.

Dataset Information

Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity.

Background

Methods

Results

Conclusion

Publications

Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity.

Similar Datasets

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