Filaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis - 04/12/15
, Sanja Kezic, PhD d, ⁎, ‡ Abstract |
Background |
Loss-of-function (LOF) mutations in the filaggrin gene (FLG) are a well-replicated risk factor for atopic dermatitis (AD) and are known to cause an epidermal barrier defect. The nature of this barrier defect is not fully understood. Patients with AD with FLG LOF mutations are known to have more persistent disease, more severe disease, and greater risk of food allergies and eczema herpeticum. Abnormalities in corneocyte morphology have been observed in patients with AD, including prominent villus-like projections (VP); however, these ultrastructural features have not been systematically studied in patients with AD in relation to FLG genotype and acute and convalescent status.
Objective |
We sought to quantitatively explore the relationship between FLG genotype, filaggrin breakdown products (natural moisturizing factor [NMF]), and corneocyte morphology in patients with AD.
Methods |
We studied 15 children at first presentation of AD and after 6 weeks of standard therapy. We applied atomic force microscopy to study corneocyte conformation in patients with AD stratified by FLG status and NMF level. By using a new quantitative methodology, the number of VPs per investigated corneocyte area was assessed and expressed as the Dermal Texture Index score. Corneocytes were also labeled with an anti-corneodesmosin antibody and visualized with scanning electron microscopy.
Results |
We found a strong correlation between NMF levels and Dermal Texture Index scores in both acute and convalescent states (respective r = −0.80 and −0.75, P < .001 and P = .002). Most, but not all, VPs showed the presence of corneodesmosin abundantly all over the cell surface in homozygous/compound heterozygous FLG patients and, to a lesser extent, in heterozygous and wild-type patients.
Conclusions |
NMF levels are highly correlated with corneocyte morphology in patients with AD. These corneocyte conformational changes shed further insight into the filaggrin-deficient phenotype and help explain the barrier defect in patients with AD with FLG LOF mutations.
Le texte complet de cet article est disponible en PDF.Key words : Skin barrier, transepidermal water loss, atopic dermatitis, filaggrin, corneocyte
Abbreviations used : AD, AFM, CE, DTI, FLG, LOF, NMF, SC, SEM, TEWL, VP
Plan
| Supported by the National Children's Research Centre Dublin, Ireland (to A.D.I and M.A.M.). The Centre for Dermatology and Genetic Medicine, University of Dundee, is supported by a Wellcome Trust Strategic Award (098439/Z/12/Z to W.H.I.M). The work performed by Serend-ip was supported by the German Ministry of Research grant no. 01DJ13022A (to C.R.). |
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| Disclosure of potential conflict of interest: C. Riethmuller holds a patent on analytic methods. M. A. McAleer has received research support from the National Children's Research Centre. L. E. Campbell, S. F. MacCallum, and W. H. I. McLean have received research support from the Wellcome Trust. A. D. Irvine has received research support from the National Children's Research Centre and has consultant arrangements with Regeneron. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 136 - N° 6
P. 1573 - décembre 2015 Retour au numéro
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