In this study, we identified FLG single nucleotide variations (FLG-SNVs) and evaluated the association of FLG-SNVs with clinical phenotypes including atopic dermatitis (AD)-associated minor clinical features, presence of specific allergic sensitization, and serum parameters.
Our study confirms the previous findings that FLG mutations are strongly associated with atopic eczema and confer a significant risk of allergic sensitization and asthma in the context of eczema.
Probably a variety of immunological mechanisms other than that resulting from the filaggrin system have an impact on allergic sensitization to a greater degree.
Allergic sensitization and filaggrin variants predispose to the comorbidity of eczema, asthma, and rhinitis: results from the Isle of Wight birth cohort.
The skin barrier disruptions of atopic eczema associated with loss-of-function mutations in filaggrin are thought to provide a nidus for allergic sensitization to food and aeroallergens, which can then lead to increased allergic disease.
There is a debate as to whether allergic sensitization and filaggrin gene (FLG) variants lead to eczema or FLG variants and eczema increase the risk of allergic sensitization.
Thus, filaggrin does not appear to have a downstream effect on the development of allergic disease, and it is indeed filaggrin's role in the epithelial function that is likely to determine the link between filaggrin mutations and allergic sensitisation.
Genetic epidemiological studies (family, case-control) of the association between filaggrin gene defects and allergic sensitisation or allergic disorders.
Our study reveals a functional role of LTB4-BLT1 axis in nonimmune cells, most likely lung ECs, in controlling allergic sensitization as an upstream regulator of IL-33.
In particular, we will focus on the evidence for IL-33 in the development of immune responses in the lung, including the role of IL-33-responsive immune cells that may explain susceptibility to allergic sensitization at a young age and the association between genetic variants of IL-33 and asthma in humans.
Together these observations indicate that pollen-induced recruitment of neutrophils is TLR4 and CXCR2 dependent and that recruitment of neutrophils is a critical rate-limiting event that stimulates induction of allergic sensitization and airway inflammation.
We recently reported that ragweed pollen extract (RWPE) requires Toll-like receptor 4 (TLR4) to stimulate CXCL-mediated innate neutrophilic inflammation, which in turn facilitates allergic sensitization and airway inflammation.
In mild untreated asthma, the expression of IL-33 mRNA in bronchial mucosa is related to innate immune activation and allergic sensitization to HDM, rather than epithelial damage, and correlates with FeNO.