Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum.
Filaggrin (FLG) loss of function variants have been associated with the onset and severity of atopic dermatitis and are the most common genetic association with AD.
Then, we assessed the proliferation and the production of the Th22 chemokines CCR4 and CCR10 by ICOSL-stimulated AD peripheral blood mononuclear cells (PBMCs) as well as their effects on keratinocyte filaggrin production.
The presence of loss-of-function mutations in the filaggrin gene (FLG) is the main predisposing factor for AD FLG mutations show ethnic and geographical variations, even between European populations.
Major limitations of published studies were low numbers of individuals with AD and FLG loss-of-function mutations and exposure to specific environmental factors (n=5 to 94), and variation in exposure definitions.
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.
A randomized controlled trial of an emollient with ceramide and filaggrin-associated amino acids for the primary prevention of atopic dermatitis in high-risk infants.
Overall, these results show that Tregs may participate into AD pathogenesis and that FLG null mutations exert further modifications on specific subpopulations of circulating Tregs.
Recent studies have identified a crucial role for the aryl hydrocarbon receptor (AHR) in controlling the gene expression of filaggrin and other skin barrier proteins, suggesting an underlying association between AHR and AD pathogenesis.
The discovery of the filaggrin gene was important in the emerging model for AD pathogenesis, combining skin barrier function with adaptive and innate immunity.
Recent investigations implicate disease severity and persistence, age of onset, parental atopic history, filaggrin (FLG) mutations, polysensitization, and the nonrural environment among risk factors for development of multiple atopic comorbidities in young children with AD.
Fifteen percent of atopic dermatitis (AD) liability-scale heritability could be attributed to 31 susceptibility loci identified by using genome-wide association studies, with only 3 of them (IL13, IL-6 receptor [IL6R], and filaggrin [FLG]) resolved to protein-coding variants.
Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD <i>FA</i>+ were substantially lower than in AD <i>FA</i>- and NA skin.
We then tested the impact of the choice of the most common definitions of 'cases' and 'controls' on AD prevalence estimates and associated risk factors (including filaggrin mutations) among children aged 5 years in two population-based birth cohorts: the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford.
OR10G7 expression was significantly increased in skin biopsy specimens from patients with AD compared with those from HC subjects (P = .01) and inversely correlated with FLG-1 expression (P = .009).
In particular, the barrier-defective epidermis in patients with AD with loss-of-function filaggrin mutations has increased IL-1α and IL-1β levels, but the mechanisms by which IL-1α, IL-1β, or both are induced and whether they contribute to the aberrant skin inflammation in patients with AD is unknown.