Filaggrin in atopic dermatitis (Reprinted from J Allergy Clin Immunol vol 122, pg 689-93, 2008)

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

    Research output: Contribution to journalArticlepeer-review

    138 Citations (Scopus)


    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. (Reprinted from J Allergy Clin Immunol 2008; 122: 689-93.)

    Original languageEnglish
    Pages (from-to)R2-R6
    Number of pages5
    JournalJournal of Allergy and Clinical Immunology
    Issue number3
    Publication statusPublished - Sep 2009


    • atopic dermatitis
    • barrier function
    • cornified cell envelope
    • eczema
    • epidermal differentiation complex
    • filaggrin
    • ichthyosis vulgaris
    • natural moisturizing factor
    • pH
    • proteases
    • Staphylococcus aureus
    • ECZEMA
    • RISK
    • SKIN
    • ASTHMA

    Cite this