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  • Title: Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling.
    Author: Angelova-Fischer I, Mannheimer AC, Hinder A, Ruether A, Franke A, Neubert RH, Fischer TW, Zillikens D.
    Journal: Exp Dermatol; 2011 Apr; 20(4):351-6. PubMed ID: 21410766.
    Abstract:
    BACKGROUND: Filaggrin gene (FLG) loss-of-function mutations have been shown to represent the strongest so far known genetic risk factor for atopic dermatitis (AD). Whereas the barrier characteristics in FLG mutation carriers under baseline conditions have been investigated, there are only limited data on the permeability barrier function in filaggrin-AD under compromised conditions. AIM: We investigated: (i) stratum corneum (SC) integrity/cohesion; (ii) barrier recovery after controlled mechanical and irritant-induced barrier abrogation; and (iii) the lipid composition of the non-lesional and lesional skin of AD patients harbouring the European R501X, 2282del4, 3702delG, R2447X or S3247X FLG variants. METHODS: Thirty-seven AD patients (14 FLG mutation carriers and 23 non-carriers) and 20 healthy controls participated in the study. Stratum corneum integrity/cohesion was assessed by measurement of transepidermal water loss (TEWL) and amount of removed protein following sequential tape stripping. Barrier recovery was monitored by repeated measurements of TEWL and erythema up to 96 h after barrier abrogation. Samples for lipid analysis were obtained from non-lesional and lesional skin using the cyanoacrylate method. RESULTS: Tape stripping revealed distinct genotype-related impairment of the SC integrity/cohesion. No differences in the rate of barrier recovery among the groups were found. The SC lipid analysis revealed significant differences regarding the percentage amount of cholesterol, ceramide/cholesterol ratio and triglycerides in the uninvolved skin as well as the amounts of free fatty acids, CER[EOH] and triglycerides in the skin lesions of the AD FLG mutation carriers. CONCLUSIONS: Our results provide evidence for discernible FLG-related barrier integrity phenotypes in atopic eczema.
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