Although standard therapy remains topical treatment, powerful systemic treatment options emerged in the last years. As AE is a first step in the atopic march, its prevention and appropriate treatment is essential. Extrinsic factors seem to play a major role in the development of AE.
1031 exchange uplet skin#
One hallmark of AE is a skin barrier disruption on multiple, highly interconnected levels: filaggrin mutations, increased skin pH, and a microbiome dysbiosis towards Staphylococcus aureus overgrowth are observed in addition to an abnormal type 2 immune response. In conclusion, our results indicate that genetic variants in the epidermal differentiation complex gene could contribute to the pathogenesis of atopic eczema and progression to subsequent allergic disease.Ītopic eczema (AE) is an inflammatory skin disease with involvement of genetic, immunological, and environmental factors. Additionally, in children with eczema, these genetic variants may also be considered, along with FLG mutations, as predictive biomarkers for eczema-associated asthma. These effects seem to be supplementary to the well-known associations for FLG mutations and may be modulated by gene–gene interactions.
1031 exchange uplet plus#
We demonstrated that risk variants of HRNR rs877776 and FLG2 rs12568784 were associated with atopic eczema, allergic sensitization, and susceptibility to the complex phenotype-asthma plus eczema. Genotyping for HRNR and FLG2 was performed in 188 children younger than 2 years of age, previously screened for the FLG null mutations, and followed at yearly intervals until the age of 6. The aim of this study was to investigate the association of SNPs in hornerin (HRNR) and filaggrin-2 (FLG2) genes with childhood atopic eczema, as well as other atopic phenotypes. Therefore, one challenge is to identify the risk factors associated with atopic eczema that may also be predictors of atopic disease progression. All rights reserved.Ītopic eczema is the most common chronic inflammatory skin disease of early childhood and is often the first manifestation of atopic march. Together, our FlgHrnr‐/‐ mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions. Surprisingly, although the immune system revealed no aberrations under steady‐state conditions, FlgHrnr‐/‐ mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels elicitating allergic reactions. Functionally, FlgHrnr‐/‐ mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Structurally, FlgHrnr‐/‐ mice displayed a markedly reduced granular layer and a condensed cornified layer. Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans.
Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation.īy using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double‐deficient (FlgHrnr‐/‐) mouse model lacking both genes including the intergenomic sequence.
Furthermore, both, FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Loss‐of‐function mutations of these genes constitute a risk factor for atopic dermatitis and eczema‐related asthma. Both proteins have been implicated as essential proteins for skin barrier maintenance. Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features.
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