Combined occurrence of filaggrin mutations and IL-10 or IL-13 polymorphisms predisposes to atopic dermatitis

Lesiak, Aleksandra; Kuna, Piotr; Zakrzewski, M; Geel, M. van; Bladergroen, Reno S.; Przybyłowska, Karolina; Stelmach, Iwona; Majak, Paweł; Hawro, Tomasz; Sysa-Jędrzejowska, Anna; Narbutt, Joanna

doi:10.1111/j.1600-0625.2010.01243.x

Cited by 50 publications

(53 citation statements)

References 33 publications

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“…Not only genetic skin barrier defects, but also genetic immune disorders such as Wiskott-Aldrich syndrome, show atopic manifestations (120), indicating that AD emerges in the context of both epidermal barrier- and immunity-associated genetic dysfunction. Indeed, many immunity-associated genes, e.g., Th2 and Th17 cytokines, innate immune receptors, and various chemokines, have been identified through wholegenome linkage studies of susceptibility genes for atopic diseases (75), some of which have been reported to show a multiplicative effect with FLG mutations on AD (121). It seems reasonable to suggest that immunity-associated genetic factors, as well as environmental factors, may act additively (or synergistically) to produce SC barrier defects and to promote percutaneous sensitization during the onset of AD.…”

Section: Figurementioning

confidence: 99%

Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases

Kubo¹,

Nagao²,

Amagai³

2012

J. Clin. Invest.

310

270

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Classic atopic dermatitis is complicated by asthma, allergic rhinitis, and food allergies, cumulatively referred to as atopic diseases. Recent discoveries of mutations in the filaggrin gene as predisposing factors for atopic diseases have refocused investigators' attention on epidermal barrier dysfunction as a causative mechanism. The skin's barrier function has three elements: the stratum corneum (air-liquid barrier), tight junctions (liquid-liquid barrier), and the Langerhans cell network (immunological barrier). Clarification of the molecular events underpinning epidermal barrier function and dysfunction should lead to a better understanding of the pathophysiological mechanisms of atopic diseases. IntroductionAtopic dermatitis (AD) is a chronic relapsing eczematous skin disorder that is frequently associated with elevated serum IgE levels and a family history of AD, allergic rhinitis, and/or asthma. Clinical manifestations of classic AD are dry skin and relapsing eczema, which usually start during early infancy or childhood and become complicated by food allergies, asthma, and/or allergic rhinitis during the first several years of life, in a process called "atopic march" (1). AD is highly prevalent in industrialized countries, where it affects approximately 15%-30% of children and 2%-10% of adults (2). The various observations of the disease indicate that AD has a complex etiology with genetic, immunological, and environmental aspects.Living organisms rely critically on surface barriers to isolate themselves from the external environment and to maintain homeostasis. While unicellular organisms are enclosed by cell membranes and cell walls, epithelial barrier structures, in several forms, cover the surfaces of multicellular organisms (3). In mammals, the airway and gastrointestinal tract are lined by simple epithelia covered with mucus. In contrast, the outer surface of the body is covered by a stratified epithelial cellular sheet called the epidermis, the outermost layer of which is cornified. Recent findings have shown that disruption of epithelial barrier systems are involved in the pathogenesis of immune disorders such as inflammatory bowel disease, asthma, and AD (4-12). In this review, we describe the barrier system of the epidermis, which is far more sophisticated than previously thought (13,14), and attempt to discuss its function with special focus on antigen penetration through these barriers and antigen capture by dendritic cells in the context of AD.

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Section: Figurementioning

confidence: 99%

Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases

Kubo¹,

Nagao²,

Amagai³

2012

J. Clin. Invest.

310

270

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“…These differences may be explained by effect size or ethnic limitations. We have not observed any association of 2282del4 of FLG gene mutation with early onset of AD like Lesiak et al [28], but some researches in European and Asian populations have indicated such a correlation [7,11,26].…”

Section: Discussionmentioning

confidence: 58%

Coexistence of 2282del4 FLG gene mutation and IL-18 –137G/C gene polymorphism enhances the risk of atopic dermatitis

Trzeciak¹,

Gleń²,

Rębała³

et al. 2016

pdia

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A b s t r a c tIntroduction: Atopic dermatitis (AD) pathogenesis appears in the context of the correlation between cornified envelope proteins and immunological factors. Aim: To estimate the association between FLG R501X and 2282del4 gene mutations, -137 G/C IL-18 and -1112 C/T IL-13 gene polymorphisms and their influence on AD course and the risk in the Polish population. Material and methods: One hundred and fifty-two AD patients and 123 healthy volunteers were included into the study. Amplification refractory mutation system -polymerase chain reaction method was used.

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“…Chen and Zhao carried out a meta-analysis of seven studies of the SNP that we found seemed to protect children against AD that considered a total of more than 800 AD subjects and about 1200 controls, 50 and found no direct association between IL10-rs 1800896 and susceptibility to, or the severity of AD, whereas Sohn et al 51 and Lesiak et al 52 have found close relationships between some IL10 promoter haplotypes and susceptibility to AD, and Lesiak et al have also found increased serum concentrations of IL10 in AD subjects with this SNP. 53 Moreover, Raedler et al found that carriers of three IL10 SNP blocks and distal promoter SNPs (including IL10-rs1800872) showed reduced levels of the expression of T reg cell markers, reduced IL-5, TNF-α and GM-CSF levels, and partially increased IFN-γ levels, and that the same SNPs were associated with the development of AD in 3-year-old children, 54 whereas Kijohara et al did not find any relationship between IL10 genetic variations and AD.…”

Section: Discussionmentioning

confidence: 99%

Impact of genetic polymorphisms on paediatric atopic dermatitis

Esposito

Patria

Spena

et al. 2015

Int J Immunopathol Pharmacol

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In order to investigate whether polymorphisms of genes encoding some factors of innate and adaptive immunity play a role in the development of, or protection against atopic dermatitis (AD) and condition its severity, we genotyped 33 candidate genes and 47 single nucleotide polymorphisms (SNPs) using Custom TaqMan Array Microfluidic Cards and an ABI 7900HT analyser (Applied Biosystems, Foster City, CA, USA). The study involved 104 children with AD (29 with mild-to-moderate and 75 with severe disease; 42 girls; mean age ± SD, 5.8 ± 3.3 years) and 119 healthy controls (49 girls; mean age, 4.8 ± 3.0 years). IL10-rs1800872T, TG and MBL2-rs500737AG were all significantly more frequent among the children with AD (P = 0.015, P = 0.004 and P = 0.030), whereas IL10-rs1800896C and TC were more frequent in those without AD (P = 0.028 and P = 0.032). The VEGFA-rs2146326A and CTLA4-rs3087243AG SNPs were significantly more frequent in the children with mild/moderate AD than in those with severe AD (P = 0.048 and P = 0.036). IL10-rs1800872T and TG were significantly more frequent in the children with AD and other allergic diseases than in the controls (P = 0.014 and P = 0.007), whereas IL10-rs1800896TC and C were more frequent in the controls than in the children with AD and other allergic diseases (P = 0.0055 and P = 0.0034). These findings show that some of the polymorphisms involved in the immune response are also involved in some aspects of the development and course of AD and, although not conclusive, support the immunological hypothesis of the origin of the inflammatory lesions.

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Combined occurrence of filaggrin mutations and IL-10 or IL-13 polymorphisms predisposes to atopic dermatitis

Cited by 50 publications

References 33 publications

Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases

Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases

Coexistence of 2282del4 FLG gene mutation and IL-18 –137G/C gene polymorphism enhances the risk of atopic dermatitis

Impact of genetic polymorphisms on paediatric atopic dermatitis

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