Filaggrin‐2 barrier protein inversely varies with skin inflammation

Seykora, John T.; Dentchev, Tzvete; Margolis, David J.

doi:10.1111/exd.12749

Cited by 24 publications

(16 citation statements)

References 10 publications

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“…They also confirm the results of Pellerin et al (16), who reported that lowered expression of FLG and FLG2 in AD skin was observed in a subgroup of patients who did not carry FLG mutations. This is in line with another study, which reported that the FLG2 protein was diminished in the presence of inflammatory mediators in AD (18) and might support the outside-inside-outside model of AD pathogenesis. Furthermore, decreased levels of FLG and FLG2 protein in non-lesional AD skin, especially in subjects without FLG mutations, may confirm that the clinically unaffected skin of patients with AD is abnormal and involved in the inflammation process.…”

Section: Discussionsupporting

confidence: 92%

Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype

Trzeciak

Sakowicz-Burkiewicz²,

Wesserling³

et al. 2017

Acta Derm Venerol

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Changes in the expression of cornified envelope (CE) proteins are thought to affect the development and course of atopic dermatitis (AD). The aim of this study was to examine the expression level of CE proteins in order to identify new molecular markers of the AD phenotype. Expression levels of CE proteins were evaluated in the skin of patients with AD (38 biopsies) and healthy subjects (26 biopsies). Levels of FLG, FLG2 and SPRR3 mRNAs and proteins were reduced in AD skin. Levels of LELP-1 and SPRR1A transcripts and proteins were significantly increased in AD skin. SPRR3v2 mRNA level in non-lesional AD skin correlated with severity of AD, and SPRR3 protein level in non-lesional AD skin correlated inversely with pruritus. FLG protein level in AD skin correlated inversely with severity of AD. These results point to SPRR3 as an important factor in AD and itch.

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Section: Discussionsupporting

confidence: 92%

Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype

Trzeciak

Sakowicz-Burkiewicz²,

Wesserling³

et al. 2017

Acta Derm Venerol

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“…AA children with a FLG‐2 loss‐of‐function mutation or non‐synonymous variant were 50% more likely to have persistent AD, but there was no effect on incidence, age of onset or disease severity . These results are consistent with a recent study demonstrating a correlation between decreased FLG‐2 expression in the skin and active skin inflammation due to AD . Interestingly, initial studies in Europeans failed to identify an association between FLG‐2 and AD, which is consistent with known differences in gene expression patterns between European, African and Asian skin …”

Section: Aetiology and Genetics Of Atopic Dermatitis In Non‐european supporting

confidence: 86%

Atopic dermatitis in diverse racial and ethnic groups—Variations in epidemiology, genetics, clinical presentation and treatment

Kaufman

Guttman‐Yassky

Alexis

2018

Experimental Dermatology

270

263

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Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects diverse ethnic groups with varying prevalence. Despite a predominance of studies in individuals of European ancestry, AD has been found to occur more frequently in Asian and Black individuals than Whites. Therefore, an understanding of the unique clinical features of AD in diverse ethnic groups, as well as the differences in genetic polymorphisms that influence susceptibility to AD and response to current therapies, is paramount for management of an increasingly diverse patient population. In this article, we review key nuances in the epidemiology, pathophysiology, clinical presentation and treatment of AD in non-White ethnic groups, which are largely underappreciated in the literature. We highlight the need for studies evaluating the tissue molecular and cellular phenotypes of AD in non-White patients, as well as greater inclusion of minority groups in clinical trials, to develop targeted treatments for a multi-ethnic population.

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“…As has been recently noted, inflamed skin has diminished FLG production not specifically associated with FLG variation. (Pellerin et al ., 2013; Seykora et al ., 2015) In addition, as expected, children with FLG LoF mutations had more persistent disease. It is probable that all of the FLG LoF variants do have a profound effect on the production of FLG and skin barrier function.…”

Section: Discussionmentioning

confidence: 99%

Uncommon Filaggrin Variants Are Associated with Persistent Atopic Dermatitis in African Americans

Margolis

Mitra

Gochnauer

et al. 2018

Journal of Investigative Dermatology

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Atopic dermatitis (AD) is a common illness that has been associated with filaggrin gene (FLG) loss of function (LoF) variation. In African Americans, a group that commonly has AD and has not been well studied, FLG LoF variation is rarely found. Our objective was to use massively parallel sequencing to evaluate FLG LoF variation in children of African ancestry to evaluate the association between FLG LoF variation and AD and AD persistence. We studied 262 African American children with AD. Nine unique FLG exon 3 LoF variants were identified for an overall minor variant frequency of 6.30% (95% confidence interval [CI] = 4.37-8.73). The most common variants were p.R501X (1.72%, 95% CI = 0.79-3.24), p.S3316X (1.34%, 95% CI = 0.54-2.73), and p.R826X (0.95%, 95% CI = 0.31-2.2). Over an average follow-up period of 96.4 (95% CI = 92.0-100.8) months, African American children with FLG LoF were less likely to be symptom free (odds ratio = 0.36, 95% CI = 0.14-0.89, P = 0.027) compared with a FLG wild-type child. In contrast to previous reports, uncommon FLG LoF variants in African American children exist and are associated with AD and more persistent AD. In contrast to Europeans, no FLG LoF variants predominate in African American children. Properly determining FLG LoF status requires advanced sequencing techniques.

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Filaggrin‐2 barrier protein inversely varies with skin inflammation

Cited by 24 publications

References 10 publications

Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype

Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype

Atopic dermatitis in diverse racial and ethnic groups—Variations in epidemiology, genetics, clinical presentation and treatment

Uncommon Filaggrin Variants Are Associated with Persistent Atopic Dermatitis in African Americans

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