Filaggrin null mutations associate with increased frequencies of allergen-specific CD4+ T-helper 2 cells in patients with atopic eczema.
McPherson T., Sherman VJ., Aslam A., Crack L., Chan H., Lloyd-Lavery A., Jones L., Ardern-Jones M., Ogg G.
BACKGROUND: Filaggrin null mutations associate with atopic eczema and also with asthma when present with eczema. However, while epidermal dysfunction is an important factor in disease pathogenesis, it is unclear how such dysfunction interacts with immune responses to contribute to cutaneous and other inflammatory atopic disease. OBJECTIVES: To gain a better understanding of the mechanisms underlying such predisposition in order to understand different disease phenotypes and possibly identify potential treatment targets. METHODS: We studied 33 individuals with atopic eczema and used interleukin-4 immunospot and human leucocyte antigen class II tetrameric complexes to investigate the peripheral blood allergen-specific CD4+ T-cell responses. RESULTS: Filaggrin null mutations associated with significantly (P<0·05) higher frequencies of allergen-specific CD4+ T-helper 2 cell responses. CONCLUSIONS: These data would support a model where barrier dysfunction possibly promotes greater allergen penetration and delivery to drive allergen-specific CD4+ T cells. This could further contribute to respiratory and cutaneous inflammatory disease.