Filaggrin in atopic dermatitis

Grainne M. O'Regan, Aileen Sandilands, W. H. Irwin McLean, Alan D. Irvine

    Research output: Contribution to journalReview article

    224 Citations (Scopus)

    Abstract

    The recent identification of loss-of-function mutations in the structural protein filaggrin as a widely replicated major risk factor for eczema sheds new light on disease mechanisms in eczema, a disease that had heretofore largely been considered to have a primarily immunologic etiopathogenesis. The filaggrin gene (FLG) mutation findings are consistent with a recently proposed unifying hypothesis that offers a mechanistic understanding of eczema pathogenesis synthesizing a heritable epithelial barrier defect and resultant diminished epidermal defense mechanisms to allergens and microbes, followed by polarized T(H)2 lymphocyte responses with resultant chronic inflammation, including autoimmune mechanisms. Although compelling evidence from genetic studies on FLG implicates perturbed barrier function as a key player in the pathogenesis of eczema in many patients, much is still unknown about the sequence of biologic, physicochemical, and aberrant regulatory events that constitute the transition from an inherited barrier defect to clinical manifestations of inflammatory eczematous lesions and susceptibility to related atopic disorders. The exact contribution of FLG to the wider atopic story, factors modifying FLG expression, and the role of other barrier proteins remain to be delineated. In this review we highlight recent advances in our understanding of the FLG genetics in the cause of eczema and related complex diseases.

    Original languageEnglish
    Pages (from-to)689-693
    Number of pages5
    JournalJournal of Allergy and Clinical Immunology
    Volume122
    Issue number4
    DOIs
    Publication statusPublished - Oct 2008

    Keywords

    • atopic dermatitis
    • barrier function
    • cornified cell envelope
    • eczema
    • epidermal differentiation complex
    • filaggrin
    • ichthyosis vulgaris
    • natural moisturizing factor
    • pH
    • proteases
    • Staphylococcus aureus
    • OF-FUNCTION MUTATIONS
    • ICHTHYOSIS VULGARIS
    • EPIDERMAL BARRIER
    • GENE
    • ECZEMA
    • RISK
    • SKIN
    • ASTHMA
    • PREDISPOSE
    • POPULATION

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