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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:126

Article

O'Regan, Grainne M.^1,2  Kemperman, Patrick M. J. H.³  Sandilands, Aileen⁴  Chen, Huijia⁴  Campbell, Linda E.⁴  Kroboth, Karin⁴  Watson, Rosemarie¹  Rowland, Marion^2,5  Puppels, Gerwin J.^3,7  McLean, W. H. Irwin⁴  Caspers, Peter J.^3,7  Irvine, Alan D.^1,2,6 

[1] Our Ladys Hosp Sick Children, Dept Paediat Dermatol, Dublin 12, Ireland

[2] Our Ladys Hosp Sick Children, Natl Childrens Res Ctr, Dublin 12, Ireland

[3] Erasmus MC, Dept Dermatol & Venerol, Ctr Opt Diagnost & Therapy, Rotterdam, Netherlands

[4] Univ Dundee, Inst Med Sci, Epithelial Genet Grp, Dundee, Scotland

[5] UCD Sch Med & Med Sci, Dublin, Ireland

[6] Trinity Coll Dublin, Dept Med, Dublin, Ireland

[7] River Diagnost BV, Rotterdam, Netherlands

关键词: Atopic dermatitis;    confocal Raman spectroscopy;    eczema;    filaggrin;    hyperlinearity;    natural moisturizing factor;    transepidermal water loss;    tyrosine;   

DOI  :  10.1016/j.jaci.2010.04.038

来源: Elsevier

【 摘 要 】

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.)

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