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dc.contributor.authorIRVINE, ALANen
dc.date.accessioned2015-11-05T15:26:10Z
dc.date.available2015-11-05T15:26:10Z
dc.date.issued2015en
dc.date.submitted2015en
dc.identifier.citationRiethmuller C, McAleer MA, Koppes SA, Abdayem R, Franz J, Haftek M, Campbell LE, MacCallum SF, McLean WH, Irvine AD, Kezic S, Filaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis., The Journal of allergy and clinical immunology, 2015en
dc.identifier.issn0091-6749en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/74850
dc.descriptionPUBLISHEDen
dc.description.abstractLoss-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.en
dc.relation.ispartofseriesThe Journal of allergy and clinical immunologyen
dc.rightsYen
dc.subjectSkin barrieren
dc.subjecttransepidermal water lossen
dc.subjectatopic dermatitisen
dc.subjectfilaggrinen
dc.subjectcorneocyteen
dc.titleFilaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/irvineaen
dc.identifier.rssinternalid107261en
dc.identifier.doihttp://dx.doi.org/10.1016/j.jaci.2015.04.042en
dc.rights.ecaccessrightsopenAccess
dc.identifier.orcid_id0000-0002-9048-2044en


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