Loss-of-Function Mutations in the Filaggrin Gene and Allergic Contact Sensitization to Nickel

Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Journal of Investigative Dermatology (Impact Factor: 7.22). 07/2008; 128(6):1430-5. DOI: 10.1038/sj.jid.5701190
Source: PubMed


Allergic contact dermatitis is one of the most frequent dermatological problems affecting 7% of the general population. Impaired skin barrier function facilitates the penetration of contact allergens and irritants into the epidermal layer and is regarded as an important cofactor promoting the process of allergic contact sensitization. Filaggrin is crucial for the maintenance of the skin barrier function. Loss-of-function mutations within the filaggrin (FLG) gene are associated with skin barrier diseases such as ichthyosis vulgaris and atopic eczema (AE). To assess the impact of FLG on allergic contact sensitization and plausible intermediate traits, the two prevalent FLG mutations R501X and 2282del4 were typed in 1,502 individuals of the KORA C population-based cohort with extensive dermatologic phenotyping. Associations of FLG mutations with AE could be replicated. Strong associations were seen with dry skin, palmar hyperlinearity, and keratosis pilaris. In addition, an association with contact sensitization to nickel and contact sensitization to nickel combined with intolerance to fashion jewelry, but not with other contact allergens, was observed. From these data, we conclude that a genetically determined FLG deficiency manifests as dry skin and features of ichthyosis vulgaris. In addition, FLG deficiency may also represent a risk factor for contact sensitization to allergens.

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Available from: Joachim Heinrich, Mar 19, 2014
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    • "It was also observed in the study that the presence of an FLG gene mutation may be the cause of lowering the age at which the allergy induced by contact with nickel sulphate occurs. It has been also confirmed that the existence of a mutation in the FLG gene and body piercing at an early age may increase the risk of a more rapid allergic and inflammatory reactions induced by nickel haptens and may cause retention of those conditions in adult patients as well [48–50]. "
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    • "Besides the intrinsic hazard of a chemical to induce skin sensitization, the risk of becoming sensitized is infl uenced by factors that increase susceptibility to acquire ACD. These include a compromised skin barrier through mutations in fi laggrin (de Jongh et al. 2008, Novak et al. 2008, Thyssen et al. 2008), and altered metabolism of the enzymes N -acetyltransferase 1 and 2 ( NAT1 and NAT2 ). These enzymes have an important role in the detoxifi cation and bioactivation of chemicals through N -acetylation and N-O -acetylation (Najim et al. 2005, Schnuch et al. 1998, Nacak et al. 2006). "
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    • "Recent findings have shown that disruption of epidermal barrier systems, for example, filaggrin deficiency, is involved in the pathogenesis of atopic diseases via augmented percutaneous sensitization with allergens that penetrate the body through the abrogated barrier of the SC1234. Contact sensitization against small metal ions such as nickel has been associated with filaggrin deficiency, suggesting that filaggrin deficiency affects the barrier properties of the SC even against small metal ions567. "
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