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

    Cite this

    O'Regan, Grainne M. ; Kemperman, Patrick M. J. H. ; Sandilands, Aileen ; Chen, Huijia ; Campbell, Linda E. ; Kroboth, Karin ; Watson, Rosemarie ; Rowland, Marion ; Puppels, Gerwin J. ; McLean, W. H. Irwin ; Caspers, Peter J. ; Irvine, Alan D. / Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes. In: Journal of Allergy and Clinical Immunology. 2010 ; Vol. 126, No. 3. pp. 574-U270.
    @article{2d30bfeaf8d84dcab748a66455156e66,
    title = "Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes",
    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.)",
    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",
    author = "O'Regan, {Grainne M.} and Kemperman, {Patrick M. J. H.} and Aileen Sandilands and Huijia Chen and Campbell, {Linda E.} and Karin Kroboth and Rosemarie Watson and Marion Rowland and Puppels, {Gerwin J.} and McLean, {W. H. Irwin} and Caspers, {Peter J.} and Irvine, {Alan D.}",
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    language = "English",
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    }

    O'Regan, GM, Kemperman, PMJH, Sandilands, A, Chen, H, Campbell, LE, Kroboth, K, Watson, R, Rowland, M, Puppels, GJ, McLean, WHI, Caspers, PJ & Irvine, AD 2010, 'Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes', Journal of Allergy and Clinical Immunology, vol. 126, no. 3, pp. 574-U270. https://doi.org/10.1016/j.jaci.2010.04.038

    Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes. / O'Regan, Grainne M.; Kemperman, Patrick M. J. H.; Sandilands, Aileen; Chen, Huijia; Campbell, Linda E.; Kroboth, Karin; Watson, Rosemarie; Rowland, Marion; Puppels, Gerwin J.; McLean, W. H. Irwin; Caspers, Peter J.; Irvine, Alan D.

    In: Journal of Allergy and Clinical Immunology, Vol. 126, No. 3, 09.2010, p. 574-U270.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes

    AU - O'Regan, Grainne M.

    AU - Kemperman, Patrick M. J. H.

    AU - Sandilands, Aileen

    AU - Chen, Huijia

    AU - Campbell, Linda E.

    AU - Kroboth, Karin

    AU - Watson, Rosemarie

    AU - Rowland, Marion

    AU - Puppels, Gerwin J.

    AU - McLean, W. H. Irwin

    AU - Caspers, Peter J.

    AU - Irvine, Alan D.

    PY - 2010/9

    Y1 - 2010/9

    N2 - 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.)

    AB - 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.)

    KW - Atopic dermatitis

    KW - confocal Raman spectroscopy

    KW - eczema

    KW - filaggrin

    KW - hyperlinearity

    KW - natural moisturizing factor

    KW - transepidermal water loss

    KW - tyrosine

    KW - OF-FUNCTION MUTATIONS

    KW - EPIDERMAL BARRIER FUNCTION

    KW - CAUSE ICHTHYOSIS VULGARIS

    KW - DRY SKIN

    KW - COMPREHENSIVE ANALYSIS

    KW - POLYETHYLENE-GLYCOLS

    KW - PROFILAGGRIN GENE

    KW - UNINVOLVED SKIN

    KW - SCHOOL-CHILDREN

    KW - MOLECULAR-LEVEL

    U2 - 10.1016/j.jaci.2010.04.038

    DO - 10.1016/j.jaci.2010.04.038

    M3 - Article

    VL - 126

    SP - 574-U270

    JO - Journal of Allergy and Clinical Immunology

    JF - Journal of Allergy and Clinical Immunology

    SN - 0091-6749

    IS - 3

    ER -