Naslov
Skin barrier function in healthy subjects and patients with atopic dermatitis in relation to filaggrin loss-of-function mutations

Autori
Jakasa Ivone ; Calkoen Florentine, Koster Elle, Bos Jan D, Verberk Maarten M, Kezic Sanja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
New trends in allergy VII and 6th Georg Rajka Symposium

Mjesto i datum
München, Njemačka, 22.07.2010. - 24.07.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
atopic dermatitis; polyethylene glycol; skin penetration; flaggrin loss-of-function mutation

Sažetak
Patients with atopic dermatitis (AD) have a defective skin barrier even in non-lesional skin as demonstrated by increased trans-epidermal water loss (TEWL) and enhanced percutaneous penetration of both lipophilic and hydrophilic compounds. The well established association between filaggrin (FLG) mutations and AD supports the hypothesis that intrinsically impaired skin barrier may be a primary step in development of AD. This seems plausible as filaggrin is a key epidermal protein which regulates several functions critical for the structure and composition of the SC. Contrasting findings have been reported on influence of FLG mutations on the skin barrier in AD. Furthermore, as only 1/3 of AD patients have FLG loss-off-function mutations, this mutations can explain the barrier abnormalities only in a subset of AD patients. In most studies related to AD, skin barrier function was assessed by measuring TEWL. It is still unclear whether TEWL is also a good parameter of the skin barrier for ingress of compounds. Enhanced TEWL and increased diffusivity of PEG370 observed in the present study suggest impairment of the skin barrier in both directions. This was further supported by a positive correlation between TEWL and D/L2. In summary, this study demonstrated reduced skin barrier in AD patients irrespective of FLG genotype, implying that also other factors than FLG loss-of-function mutations modulate skin barrier integrity. Enhanced TEWL and diffusivity in AD suggests defects in the intercellular lipid bilayers of the SC. The mechanisms underlying disturbance of lipid organization in the SC might be different in AD patients with and without FLG mutations. It would be therefore interesting to investigate the composition as well as the organization of intercellular lipids of the SC in AD patients in relation to FLG genotype and state of disease.

Izvorni jezik
Engleski

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