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


OBJECTIVE
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.
O'Regan
Gráinne M
GM
National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.
Kemperman
Patrick M J H
PM
Sandilands
Aileen
A
Chen
Huijia
H
Campbell
Linda E
LE
Kroboth
Karin
K
Watson
Rosemarie
R
Rowland
Marion
M
Puppels
Gerwin J
GJ
McLean
W H Irwin
WH
Caspers
Peter J
PJ
Irvine
Alan D
AD
D002648:Child; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D007494:Ireland; D008297:Male; D009154:Mutation; D010641:Phenotype; D012867:Skin / Q000378:metabolism*; D013059:Spectrum Analysis, Raman
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins