Lack of Filaggrin Expression in the Human Bronchial Mucosa

Abstract

RATIONALE: Deficiency of expression of filaggrin, a protein expressed by keratinocytes in the stratum corneum of the skin, predisposes to atopic dermatitis and icthyosis by increasing skin permeability. A recent study suggested that filaggrin deficient subjects who develop atopic dermatitis, but not those who do not, are also at increased risk of atopic asthma. We wished to address the hypothesis that filaggrin is expressed in the bronchial mucosa as in the skin and that deficiency is associated with asthma. METHODS: Filaggrin immunoreactivity was sought in sections of bronchial biopsies from mild asthmatics and normal controls (n=7 each), and in sections of skin biopsies from healthy atopic subjects 6 hours after intradermal challenge with allergen or diluent control (n=3). Two different primary anti-filaggrin antibodies were used in standard immunohistochemical protocols. RESULTS: Filaggrin immunoreactivity was clearly detectable at the base of the stratum corneum in section s of the skin biopsies from all 3 subjects. There was no discernable difference in expression following allergen challenge. In contrast, filaggrin immunoreactivity was undetectable in sections of bronchial biopsies from all 7 asthmatics and controls. CONCLUSIONS: Filaggrin cannot play a role in regulation of water and allergen permeability in the bronchial mucosa as it does in the skin. The fact, however, that filaggrin deficient patients with atopic dermatitis are also at increased risk of asthma suggests the possibility that the latter may in part reflect transdermal allergen sensitisation.