Severe skin inflammation and filaggrin mutation similarly alter the skin barrier in patients with atopic dermatitis

G. Mõcsai, K. Gáspár, G. Nagy, B. Irinyi, A. Kapitány, T. Bíró, E. Gyimesi, B. Tóth, L. Máródi, A. Szegedi

Research output: Article

23 Citations (Scopus)

Abstract

Background Filaggrin (FLG) deficiency is a well-known predisposing factor for the development of atopic dermatitis (AD). Decreased FLG expression can be the result of haploinsufficiency or severe inflammation, which can cause acquired FLG alterations. FLG mutations are related to several clinical and laboratory parameters of AD; however, some recent data seem to contradict these associations. Objectives Our aim was to determine which clinical and biochemical parameters are connected to FLG haploinsufficiency and which ones are also associated with acquired FLG alterations due to severe skin symptoms in patients with AD. Methods We introduced a novel classification of patients with AD, based on FLG mutations and SCORAD (SCORing Atopic Dermatitis). Based on these parameters, we created three groups of patients with AD: mild-to-moderate wild-type (A), severe wild-type (B) and severe mutant (C). In all groups, we assessed laboratory and clinical parameters and performed immunohistochemical analyses. Results Groups B and C contained patients with equally severe symptoms based on the SCORAD. The two severe groups did not differ significantly with respect to barrier-specific parameters, whereas group A had significantly better results for the barrier function measurements. However, significant differences were detected between groups B and C with respect to the allergic sensitization-specific parameters. Conclusions These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms. Nevertheless, our results also suggest that patients with FLG mutant-type AD may have a higher risk of allergic sensitization compared with patients with the wild-type. What's already known about this topic? There is a strong genotype-phenotype link in patients with atopic dermatitis (AD) suffering from filaggrin (FLG) haploinsufficiency, but acquired FLG deficiency can also occur in patients with AD. It is not known whether the clinical and laboratory characteristics of AD are influenced only by genetic or also by acquired FLG alterations. What does this study add? Actual skin barrier impairment in patients with AD with severe skin inflammation is similar in patients with FLG wild-type and FLG mutant-type and correlates with the severity of skin inflammation (SCORing Atopic Dermatitis). On the other hand the constant barrier deficiency in patients with FLG mutant-type results in an increased risk of allergic sensitization compared with patients with the wild-type.

Original languageEnglish
Pages (from-to)617-624
Number of pages8
JournalBritish Journal of Dermatology
Volume170
Issue number3
DOIs
Publication statusPublished - 2014

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Atopic Dermatitis
Inflammation
Skin
Mutation
Haploinsufficiency
filaggrin
Causality

ASJC Scopus subject areas

  • Dermatology
  • Medicine(all)

Cite this

@article{91abd1b305544b89a266272d2e2bfd40,
title = "Severe skin inflammation and filaggrin mutation similarly alter the skin barrier in patients with atopic dermatitis",
abstract = "Background Filaggrin (FLG) deficiency is a well-known predisposing factor for the development of atopic dermatitis (AD). Decreased FLG expression can be the result of haploinsufficiency or severe inflammation, which can cause acquired FLG alterations. FLG mutations are related to several clinical and laboratory parameters of AD; however, some recent data seem to contradict these associations. Objectives Our aim was to determine which clinical and biochemical parameters are connected to FLG haploinsufficiency and which ones are also associated with acquired FLG alterations due to severe skin symptoms in patients with AD. Methods We introduced a novel classification of patients with AD, based on FLG mutations and SCORAD (SCORing Atopic Dermatitis). Based on these parameters, we created three groups of patients with AD: mild-to-moderate wild-type (A), severe wild-type (B) and severe mutant (C). In all groups, we assessed laboratory and clinical parameters and performed immunohistochemical analyses. Results Groups B and C contained patients with equally severe symptoms based on the SCORAD. The two severe groups did not differ significantly with respect to barrier-specific parameters, whereas group A had significantly better results for the barrier function measurements. However, significant differences were detected between groups B and C with respect to the allergic sensitization-specific parameters. Conclusions These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms. Nevertheless, our results also suggest that patients with FLG mutant-type AD may have a higher risk of allergic sensitization compared with patients with the wild-type. What's already known about this topic? There is a strong genotype-phenotype link in patients with atopic dermatitis (AD) suffering from filaggrin (FLG) haploinsufficiency, but acquired FLG deficiency can also occur in patients with AD. It is not known whether the clinical and laboratory characteristics of AD are influenced only by genetic or also by acquired FLG alterations. What does this study add? Actual skin barrier impairment in patients with AD with severe skin inflammation is similar in patients with FLG wild-type and FLG mutant-type and correlates with the severity of skin inflammation (SCORing Atopic Dermatitis). On the other hand the constant barrier deficiency in patients with FLG mutant-type results in an increased risk of allergic sensitization compared with patients with the wild-type.",
author = "G. M{\~o}csai and K. G{\'a}sp{\'a}r and G. Nagy and B. Irinyi and A. Kapit{\'a}ny and T. B{\'i}r{\'o} and E. Gyimesi and B. T{\'o}th and L. M{\'a}r{\'o}di and A. Szegedi",
year = "2014",
doi = "10.1111/bjd.12743",
language = "English",
volume = "170",
pages = "617--624",
journal = "British Journal of Dermatology",
issn = "0007-0963",
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TY - JOUR

T1 - Severe skin inflammation and filaggrin mutation similarly alter the skin barrier in patients with atopic dermatitis

AU - Mõcsai, G.

AU - Gáspár, K.

AU - Nagy, G.

AU - Irinyi, B.

AU - Kapitány, A.

AU - Bíró, T.

AU - Gyimesi, E.

AU - Tóth, B.

AU - Máródi, L.

AU - Szegedi, A.

PY - 2014

Y1 - 2014

N2 - Background Filaggrin (FLG) deficiency is a well-known predisposing factor for the development of atopic dermatitis (AD). Decreased FLG expression can be the result of haploinsufficiency or severe inflammation, which can cause acquired FLG alterations. FLG mutations are related to several clinical and laboratory parameters of AD; however, some recent data seem to contradict these associations. Objectives Our aim was to determine which clinical and biochemical parameters are connected to FLG haploinsufficiency and which ones are also associated with acquired FLG alterations due to severe skin symptoms in patients with AD. Methods We introduced a novel classification of patients with AD, based on FLG mutations and SCORAD (SCORing Atopic Dermatitis). Based on these parameters, we created three groups of patients with AD: mild-to-moderate wild-type (A), severe wild-type (B) and severe mutant (C). In all groups, we assessed laboratory and clinical parameters and performed immunohistochemical analyses. Results Groups B and C contained patients with equally severe symptoms based on the SCORAD. The two severe groups did not differ significantly with respect to barrier-specific parameters, whereas group A had significantly better results for the barrier function measurements. However, significant differences were detected between groups B and C with respect to the allergic sensitization-specific parameters. Conclusions These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms. Nevertheless, our results also suggest that patients with FLG mutant-type AD may have a higher risk of allergic sensitization compared with patients with the wild-type. What's already known about this topic? There is a strong genotype-phenotype link in patients with atopic dermatitis (AD) suffering from filaggrin (FLG) haploinsufficiency, but acquired FLG deficiency can also occur in patients with AD. It is not known whether the clinical and laboratory characteristics of AD are influenced only by genetic or also by acquired FLG alterations. What does this study add? Actual skin barrier impairment in patients with AD with severe skin inflammation is similar in patients with FLG wild-type and FLG mutant-type and correlates with the severity of skin inflammation (SCORing Atopic Dermatitis). On the other hand the constant barrier deficiency in patients with FLG mutant-type results in an increased risk of allergic sensitization compared with patients with the wild-type.

AB - Background Filaggrin (FLG) deficiency is a well-known predisposing factor for the development of atopic dermatitis (AD). Decreased FLG expression can be the result of haploinsufficiency or severe inflammation, which can cause acquired FLG alterations. FLG mutations are related to several clinical and laboratory parameters of AD; however, some recent data seem to contradict these associations. Objectives Our aim was to determine which clinical and biochemical parameters are connected to FLG haploinsufficiency and which ones are also associated with acquired FLG alterations due to severe skin symptoms in patients with AD. Methods We introduced a novel classification of patients with AD, based on FLG mutations and SCORAD (SCORing Atopic Dermatitis). Based on these parameters, we created three groups of patients with AD: mild-to-moderate wild-type (A), severe wild-type (B) and severe mutant (C). In all groups, we assessed laboratory and clinical parameters and performed immunohistochemical analyses. Results Groups B and C contained patients with equally severe symptoms based on the SCORAD. The two severe groups did not differ significantly with respect to barrier-specific parameters, whereas group A had significantly better results for the barrier function measurements. However, significant differences were detected between groups B and C with respect to the allergic sensitization-specific parameters. Conclusions These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms. Nevertheless, our results also suggest that patients with FLG mutant-type AD may have a higher risk of allergic sensitization compared with patients with the wild-type. What's already known about this topic? There is a strong genotype-phenotype link in patients with atopic dermatitis (AD) suffering from filaggrin (FLG) haploinsufficiency, but acquired FLG deficiency can also occur in patients with AD. It is not known whether the clinical and laboratory characteristics of AD are influenced only by genetic or also by acquired FLG alterations. What does this study add? Actual skin barrier impairment in patients with AD with severe skin inflammation is similar in patients with FLG wild-type and FLG mutant-type and correlates with the severity of skin inflammation (SCORing Atopic Dermatitis). On the other hand the constant barrier deficiency in patients with FLG mutant-type results in an increased risk of allergic sensitization compared with patients with the wild-type.

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