Decreased expression of filaggrin in atopic skin

Seguchi, Tokuji; Cui, Chang‐Yi; Kusuda, Shigeru; Takahashi, Masahide; Aisu, Kinue; Tezuka, Tadashi

doi:10.1007/bf02505232

Cited by 163 publications

(119 citation statements)

References 31 publications

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“…A breakdown product of filaggrin, natural moisturizing factor, acts in retaining moisture and further contributes to the hydration of the skin. Before the identification of filaggrin null mutations (FLG), decreased expression of filaggrin has been shown in AD (9 Since then, more than 30 independent studies worldwide have confirmed the association of FLG with AD. However, the majority of AD patients do not carry FLG.…”

Section: Filaggrin Mutations: Evidence For Physical Barrier Defects Amentioning

confidence: 99%

New insights in the pathogenesis of atopic dermatitis

Ong

2013

Pediatr Res

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Section: Filaggrin Mutations: Evidence For Physical Barrier Defects Amentioning

confidence: 99%

New insights in the pathogenesis of atopic dermatitis

Ong

2013

Pediatr Res

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“…The well-known clinical association between IV and AD and the previously observed decrease of filaggrin expression in AD [57,58] suggested that FLG loss-of-function mutations might also be of relevance for AD. Subsequently, Palmer et al showed that both the R501X and 2282del4 alleles are strong predisposing factors for AD [59]; following this initial report an impressive series of independent replication studies (for reviews, see [55,60,61]) has provided unequivocal evidence that FLG null alleles are major risk factors for AD.…”

Section: Filaggrinmentioning

confidence: 94%

Clinical Impact of Current Genetics Findings

Weidinger¹,

Kabesch²

2011

Pediatric and Adolescent Medicine

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Atopic dermatitis (AD) is the one of the most common chronic skin diseases with prevalence rates of up to 20% in young infants and children and up to 5% in adults. The majority of patients show an onset of disease in early childhood and a spontaneous remission until adolescence, but there might be relapses, and the disease can also start in or persist into adulthood. AD presents a wide spectrum of clinical patterns and a variety of trigger factors with variable importance in the individual patient. It is frequently accompanied by elevated levels of total serum IgE antibodies and IgEmediated responses to common allergens, and often co-occurs with other allergic disorders such as food allergy, asthma and rhinitis, giving further rise to possible subpopulations of patients [1].Since there is no objective laboratory test or histologic finding specific for AD, diagnosis is usually made on the basis of a dermatologic examination of skin lesions considering their age-specific morphology and distribution. Further signs leading to the diagnosis of AD are the chronicity of symptoms and their association with pruritus [2]. For large epidemiologic studies, numerous diagnostic criteria have been developed in order to establish a definition for AD by using reliable discriminators resulting in increased validity and reproducibility of the diagnosis of AD. At present, the UK diagnostic criteria are most widely validated and appear to be applicable and repeatable across all ages and many ethnicities. However, as shown in a recent review, the ideal set of diagnostic criteria still has to be established [3].The pathophysiology of AD is complex and involves a disturbance of the epidermal barrier as well as abnormal immunological and inflammatory pathways leading to a Th2-dominated immune response with a Th17 component in acute AD lesions and the progressive conversion to a Th1-dominated response in chronic AD lesions [1].

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“…Recent human genetic studies strongly suggest that perturbation of the skin barrier function as a result of reduction or complete loss of filaggrin expression leads to enhanced percutaneous transfer of an allergen (47)(48)(49). The expression level of filaggrin has been known to be decreased in AD patients at both the protein and mRNA levels (50,51). The filaggrin gene defect may be the foundational predisposing factor not only for the development of eczema, but also for the initial sensitization and progression of the allergic diseases (47,48).…”

Section: Possible Evidence Of the 'Social Manner' Of Cells And Moleculesmentioning

confidence: 99%

The mechanism of atopic march may be the ‘social’ event of cells and molecules (Review)

Luo

Li²,

Gong³

2010

Int J Mol Med

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Abstract. The skin, the conjunctivae, the airways and the digestive tract compose a huge vulnerable biological surface, which is exposed to the external environment. An allergen can often trigger an allergic reaction at a number of sites or result in an atopic march. However, the mechanism of atopic march remains unclear. Less attention has been paid to the connection between the primary site and the atopic site, because current knowledge is established directly against harmful factors. Allergic hypersensitivity manifests in parts of the human body far away from the allergen. Growing evidence suggests that the epithelial cells serve as the 'engine' which initiates an allergic reaction through the production of large quantities of cytokines, chemokines and growth factors. Because the epithelial cells cover the entire surface of the skin, the conjunctivae, the airways, and the digestive tract, and are positioned at the terminals of neurons and the blood supply, the connection between the primary site and the atopic site can not be easily understood by the current knowledge of anatomy and of the neuroendocrine immune network. What is the linkage between these huge vulnerable biologic surfaces? This article highlights selected frontiers in allergy research of atopic march, and focuses on recently attained insights into the cellular and molecular events of primary and atopic lesions in the allergy progress. Special attention is paid to the homogeneity of the cellular and molecular events on the huge vulnerable surface. Based on currently available data we conclude that the skin, conjunctivae, airways and digestive tract may join together to form the frontier 'commonwealth union' in order to fight the allergen. The epithelial cells are the 'engine' as well as the main target which initiates both primary and atopic inflammatory reactions. The atopic lesion may 'duplicate' the primary contacted site of cellular and molecular events. The atopic march may be due to the intrinsic 'social' involvements of the positioned epithelial cells, but may not be totally controlled by the anatomic connection or the circulating systemic factors involved in allergy pathogenesis.

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Decreased expression of filaggrin in atopic skin

Cited by 163 publications

References 31 publications

New insights in the pathogenesis of atopic dermatitis

New insights in the pathogenesis of atopic dermatitis

Clinical Impact of Current Genetics Findings

The mechanism of atopic march may be the ‘social’ event of cells and molecules (Review)

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