The contribution of filaggrin gene mutations to atopic dermatitis has increased our appreciation of the role barrier perturbations play in inflammatory dermatoses.
Studies have shown that AD harbors different endotypes across different age groups and ethnicities and according to IgE levels and filaggrin mutation status.
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.
Although several studies have consistently found FLG loss-of-function mutations in up to 50% of European and 27% of Asian patients with AD, FLG mutations were 6 times less common in African American than in European American patients, even in patients with severe AD.
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.
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.
Lentivirus-mediated in vitro assays identified that knockdown of SHARPIN can induce elevated expression of IL-33 and its orphan receptor ST2, FLG and STAT3 and NF-κB inactivation in HaCaT keratinocytes, which has been widely evidenced in regulating AD development.
However, little is known about the contribution of loss-of-function mutations in the gene encoding filaggrin (FLG) gene, which are considered to be predisposing factors for eczema and asthma, to these associations.
To determine whether FLG mutations are associated with increased prescribing for eczema and asthma and whether increased prescribing is associated with increased healthcare costs.
Two novel FLG LOF singletons, c.488delG and p.S3101*, were discovered as well as p.R501*, p.R826* and rs149484917" genes_norm="2312">p.S3316* previously reported for AD. rs149484917" genes_norm="2312">p.S3316* (rs149484917) is likely an African ancestral FLG LOF, reported in African individuals in ExAC (Exome Aggregation Consortium), Exome Variant Server (ESP), and 4 African 1000G population databases (ESN, MSL, ASW, and ACB).
Atopic dermatitis is characterized by skin barrier defects (such as mutations in filaggrin), intrinsic proallergic T-helper cell 2 immune dysregulation, and skin microbiome alterations.
Filaggrin (FLG) genotypes were determined, and disease severity (Eczema Area and Severity Index, Rajka-Langeland Severity Score, Investigator's Global Assessment score, Numerical Rating Scale, and Dermatology Life Quality Index) was captured.