Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes

Grainne M. O'Regan, Patrick M. J. H. Kemperman, Aileen Sandilands, Huijia Chen, Linda E. Campbell, Karin Kroboth, Rosemarie Watson, Marion Rowland, Gerwin J. Puppels, W. H. Irwin McLean, Peter J. Caspers, Alan D. Irvine

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    Abstract

    Background: Filaggrin (FLG) has a central role in the pathogenesis of atopic dermatitis (AD). FLG is a complex repetitive gene; highly population-specific mutations and multiple rare mutations make routine genotyping complex. Furthermore, the mechanistic pathways through which mutations in FLG predispose to AD are unclear.

    Objectives: We sought to determine whether specific Raman microspectroscopic natural moisturizing factor (NMF) signatures of the stratum corneum could be used as markers of FLG genotype in patients with moderate-to-severe AD.

    Methods: The composition and function of the stratum corneum in 132 well-characterized patients with moderate-to-severe AD were assessed by means of confocal Raman microspectroscopy and measurement of transepidermal water loss (TEWL). These parameters were compared with FLG genotype and clinical assessment.

    Results: Three subpopulations closely corresponding with FLG genotype were identified by using Raman spectroscopy. The Raman signature of NMF discriminated between FLG-associated AD and non-FLG-associated AD (area under the curve, 0.94; 95% CI, 0.91-0.99). In addition, within the subset of FLG-associated AD, NMF distinguished between patients with 1 versus 2 mutations. Five novel FLG mutations were found on rescreening outlying patients with Raman signatures suggestive of undetected mutations (R3418X, G1138X, S1040X, 10085delC, and L2933X). TEWL did not associate with FLG genotype subgroups.

    Conclusions: Raman spectroscopy permits rapid and highly accurate stratification of FLG-associated AD. FLG mutations do not influence TEWL within established moderate-to-severe AD. (J Allergy Clin Immunol 2010;126:574-80.)

    Original languageEnglish
    Pages (from-to)574-U270
    Number of pages8
    JournalJournal of Allergy and Clinical Immunology
    Volume126
    Issue number3
    DOIs
    Publication statusPublished - Sep 2010

    Keywords

    • Atopic dermatitis
    • confocal Raman spectroscopy
    • eczema
    • filaggrin
    • hyperlinearity
    • natural moisturizing factor
    • transepidermal water loss
    • tyrosine
    • OF-FUNCTION MUTATIONS
    • EPIDERMAL BARRIER FUNCTION
    • CAUSE ICHTHYOSIS VULGARIS
    • DRY SKIN
    • COMPREHENSIVE ANALYSIS
    • POLYETHYLENE-GLYCOLS
    • PROFILAGGRIN GENE
    • UNINVOLVED SKIN
    • SCHOOL-CHILDREN
    • MOLECULAR-LEVEL

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