About a decade age, loss-of-function mutations in the filaggrin molecule were first implicated in the pathogenesis of ichthyosis vulgaris and, subsequently, of atopic dermatitis and other atopic diseases.
Enhancing filaggrin expression using ligands for the aryl hydrocarbon receptor may also be an adjunctive measure to restore the disrupted barrier function specifically for AD.
Considering the potential genetic overlap between the two diseases and the recent finding that mutations in the skin barrier protein filaggrin are associated with AD, we investigated a possible association between LCE3C_LCE3B-del and AD.
We sought to identify pathogenic pathways involved in AD by comparing the transcriptomes of AD patients stratified for filaggrin (FLG)-null mutations to those of both healthy donors and patients with ichthyosis vulgaris.
Discoveries in the defective molecular composition of the epidermal barrier, such as the epidermal protein filaggrin, in those with atopic eczema (or atopic dermatitis [AD]) have proved crucial in understanding this disease, but its aetiology remains to be fully elucidated.
The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD.
The contribution of filaggrin gene mutations to atopic dermatitis has increased our appreciation of the role barrier perturbations play in inflammatory dermatoses.
Taken together, we demonstrate that tight junction genes and, in particular, CLDN1 rather than variants in FLG may be involved in the susceptibility of AD in the Ethiopian population.
We studied the association between FLG copy number and AD in 132 Ethiopians and found no association between AD severity and FLG copy number, suggesting that other, still unidentified genetic factors are of more importance in predisposing Ethiopians to AD.
A total of 73 persons were enrolled: 21 patients with mild AD, 21 with moderate-to-severe AD, 13 with X-linked ichthyosis (XLI) as a negative control for filaggrin gene (FLG) mutation, and 18 healthy controls.
Our aim is to establish an explant HSE (Ex-HSE) for AD by using non-lesional skin from AD patients wildtype for FLG or harbouring homozygous FLG mutations.
FLG loss-of-function mutations were significantly associated with AD onset in infancy (≤2 years) (P < 0.001, OR 3.54, 95% CI 1.88-6.65), but not with AD onset in childhood (≥3 years) (P = 0.981, OR 0.99, 95% CI 0.29-3.36), and none of the children in the present cohort who developed AD at 5 years of age or later carried FLG loss-of-function mutations.
Topical Glucose Induces Claudin-1 and Filaggrin Expression in a Mouse Model of Atopic Dermatitis and in Keratinocyte Culture, Exerting Anti-inflammatory Effects by Repairing Skin Barrier Function.
Our findings highlight a novel and potentially treatable signaling axis controlling filaggrin expression and processing that is defective in patients with AD.