角蛋白10的功能与相关皮肤病

角蛋白10(keratin 10,K10)为Ⅰ型角蛋白,由KRT10基因编码,与Ⅱ型角蛋白K1配对组装成角蛋白丝,是表皮的主要结构蛋白.KRT10基因突变可导致表皮松解角化过度症、豪猪状鱼鳞病、雪花状鱼鳞病等多种遗传性皮肤病,K10也参与银屑病、毛发红糠疹、特应性皮炎等炎症性皮肤病的发病机制中.K10的功能远不只是作为...     

银屑病皮炎:一种新的疾病?

特应性皮炎(atopic dermatitis,AD)和银屑病(psoriasis,PS)都是皮肤科常见的慢性复发性炎症性皮肤病,大部分病例临床表现是明显可区分的,但部分患者可能同时具有特应性皮炎和银屑病的临床特征,有学者将其称为银屑病皮炎(psoriasis dermatitis,PD).尽管文献中没有对其存在及命名...     

寻常型鱼鳞病合并银屑病1例

1临床资料 患者男,38岁,梅州人,因双下肢皮肤干燥、脱屑36年,伴红斑、丘疹、斑块2年来我院门诊就诊。患者自两岁起双小腿皮肤干燥、脱屑,后逐渐发展至整个下肢,曾在当地医院就诊,诊断为“鱼鳞病”。2年前患者双下肢对称出现丘疹,部分融合成斑块,鳞屑明显并伴轻度瘙痒。     

特应性皮炎全基因组病学及相关候选基因的研究进展

特应性皮炎(AD)是一种常见的慢性反复性炎症皮肤疾病。遗传因素是特应性皮炎发生、发展的重要因素。目前,AD遗传易感基因位点及相关候选基因的研究已取得一定的进展,通过全基因组连锁分析等方法发现染色体3p26-22,3q13-21,15q14-21,17q21-25和18q11-12区域存在AD易感位点及相关候选基因,并与特应性皮炎发病密切相关。这些研究有利于进一步加深对AD发病机制的认识,并可能为AD的治疗提供新的方向。     

成人银屑病皮炎1例报告及文献复习

报告1例银屑病皮炎。患者男,36岁。因全身反复红斑及丘疹伴瘙痒6年余,加重2个月余就诊。皮肤科检查：头皮可见较多白色鳞屑,枕后可见红色斑块;面部弥漫性红色斑片,上覆白色鳞屑,双耳可见散在痂壳;躯干及四肢散在红色斑块,部分上覆白色鳞屑,指甲部分可见点状凹陷及甲板变形。多次皮损组织病理检查均提示银屑病特征性改变。根据临床表现及皮损组织病理检查结果,最终诊断为银屑病皮炎。     

多基因遗传性皮肤病的遗传易感性研究进展

近年来，多基因遗传性皮肤病，包括银屑病、系统性红斑狼疮、特应性皮炎和白癜风等的遗传和基因研究已取得了很大进展，对这些常见的复杂疾病已经定位到了基因水平。尤其是对银屑病遗传易感性的研究更是取得了令人瞩目的成就。综述对这4种多基因遗传性皮肤病的遗传易感性研究的最新进展。     

延边朝鲜族AD患者FLG基因SNPs与血清生化指标相关性分析

目的研究延边地区朝鲜族特应性皮炎患者丝聚蛋白基因单核苷酸多态性与血清IgE及IL-13相关性分析。方法选择70例特应性皮炎患者和90例正常对照人群作为研究对象,使用PCR法,研究丝聚蛋白基因2个SNPs位点(rs11584340及rs3126085)的基因型分布,并进行生化指标在各基因型间比较。结果延边朝鲜族特应性皮炎组血清IgE及IL-13水平显著高于正常组(P<0.01);rs11584340多态在特应性皮炎组内基因型AG有增高血清IgE趋势(P=0.05),但与IL-13不相关(P>0.05)。结论血清IgE及IL-13与延边朝鲜族人群特应性皮炎有明显相关性,是特应性皮炎的危险因素;延边朝鲜族特应性皮炎患者中rs11584340多态基因型AG有增加血清IgE趋势。     

皮肤病相关MicroRNAs表达的研究进展

MicroRNAs(miRNAs)是一种大小约18～25个核苷酸的非编码单链小RNA分子,参与包括细胞增殖、分化、凋亡、发育和逆境应答等多种生物学过程。近年来研究发现多种miRNA在皮肤生理生化免疫等过程中发挥了极其重要的作用,在某些皮肤病皮损组织中有异常表达,是皮肤病发生、发展过程中重要的调控因素。本文综述miRNAs的生物合成、作用机制、与皮肤病的相关性及研究前景,有助于进一步了解某些皮肤病的病理生理机制,为开展皮肤病miRNAs的表达及功能研究提供线索,为皮肤病早期诊断和治疗提供新的思路。     

特应性皮炎中相关细胞因子的研究进展

特应性皮炎(AD)发病机制复杂,其中免疫学功能的紊乱和调节失衡是AD发病的中心环节。本文对近年来报道的与AD发病相关的细胞因子进行综述。     

Disaggregation of Corneocytes from Surfactant-treated Sheets of Stratum Corneum in Hyperkeratosis on Psoriasis,Ichthyosis Vulgaris and Atopic Dermatitis

To elucidate the pathogenesis of impaired barrier function and the influence of surfactant on the stratum corneum in hyperkeratosis, we investigated morphological alterations of the corneocytes with soap solution. Groups of five patients each with psoriasis vulgaris (PV), ichthyosis vulgaris (IV), atopic dermatitis (AD), and normal controls were examined. Four samples of the horny layer were obtained from the same site by cyanoacrylate adhesive biopsy. The first sample was used for the superficial layer, and the fourth, for the basal horny layers. Each sample was agitated in 1% stirred soap solution at 60°C. The number and size of isolated corneocytes and the morphologic changes were investigated. The release of corneocytes was greater and the swelling and morphological changes of corneocytes exposed to soap solutions were less in PV and AD than in IV or in healthy subjects. In IV, the release was markedly less than in controls. The release and swelling were greater in the superficial than in the basal horny layers. It was concluded that the cohesiveness of corneocytes was probably less in PV and AD and greater in IV than in normals. It was also suggested that the cohesion of corneocytes from the superficial horny layer was less than that from the deep layer. The permeability of the cornified envelope in PV and AD patients was less than in IV or healthy subjects. It was confirmed that highly potent soaps induce loss of many corneocytes and reduce the barrier function of the stratum corneum.     

Analysis of Taiwanese ichthyosis vulgaris families further demonstrates differences in FLG mutations between European and Asian populations

Background  Mutations in the gene encoding filaggrin ( FLG ) were identified to underlie ichthyosis vulgaris (IV) and also shown to predispose to atopic eczema. Until now, no FLG mutations have been described in the Taiwanese population.
Objectives  To elucidate filaggrin mutations in the Taiwanese population and further to clarify the population genetics of filaggrin gene mutations in the Asian populations.
Methods  In the present study, 12 individuals from four unrelated Taiwanese IV families were examined for FLG mutations. We carried out comprehensive sequencing of the entire FLG coding region using an overlapping polymerase chain reaction strategy.
Results  We identified three FLG mutations in the Taiwanese IV families. One mutation E1795X was a previously unidentified FLG mutation, which might be specific to the Taiwanese. Interestingly, another FLG mutation 3321delA is prevalent in the Japanese population and the other mutation Q2417X was found in the Singaporean Chinese population. No FLG mutation identified in the white European population was found in the Taiwanese population.
Conclusions  The present findings suggest that the Taiwanese population, as an East Asian group, share FLG mutations with both the Japanese and the Singaporean Chinese population. In addition, these results exemplify differences in the population genetics of filaggrin between Europe and Asia.     

FLG mutations in ichthyosis vulgaris and atopic eczema: spectrum of mutations and population genetics

Filaggrin is a key protein involved in skin barrier function. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris and have been shown to be major predisposing factors for atopic eczema (AE), initially in European populations. Subsequently, FLG mutations were identified in Japanese, Chinese, Taiwanese and Korean populations. It was demonstrated that FLG mutations are closely associated with AE in the Japanese population. Notably, the same FLG mutations identified in the European population were rarely found in Asians. These results exemplify differences in filaggrin population genetics between Europe and Asia. For mutation screening, background information needs to be obtained on prevalent FLG mutations for each geographical population. It is therefore important to establish the global population genetics maps for FLG mutations. Mutations at any site within FLG, even mutations in C‐terminal imperfect filaggrin repeats, cause significant reductions in amounts of profilaggrin/filaggrin peptide in patient epidermis as the C‐terminal region is essential for proper processing of profilaggrin into filaggrin. Thus, no genotype–phenotype correlation has been observed in patients with FLG mutations. A restoration of the barrier function seems a feasible and promising strategy for treatment and prevention in individuals with filaggrin deficiency.     

On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis

Undisturbed epidermal differentiation is crucial for an intact skin barrier function. The epidermal differentiation complex (EDC) is a cluster of genes on chromosome 1q21 encoding proteins that fulfil important functions in terminal differentiation in the human epidermis, including filaggrin, loricrin, S100 proteins and others. Recently, evidence emerged that variation within EDC genes plays an important role in the pathogenesis of three common skin disorders, ichthyosis vulgaris, atopic dermatitis (AD) and psoriasis. Two loss-of-function mutations in the filaggrin (FLG) gene, R501X and 2282del4, were identified as causative for ichthyosis vulgaris in 15 affected European families, and the mode of inheritance was found to be semidominant. As ichthyosis vulgaris and AD often occur concomitantly in affected individuals, these two mutations were subsequently investigated in AD patients and found to be strongly associated with the disease. Following this first report, seven replication studies have been performed that all confirm an association of these two mutations with AD (or AD subtypes) in several European cohorts. Additionally, two unique loss-of-function mutations in the FLG gene were identified in Japanese ichthyosis vulgaris families and found to be associated with AD in a Japanese cohort. Thus, the FLG mutations are among the most consistently replicated associations for AD. Additionally, linkage analysis has suggested that variation within the EDC might also predispose for psoriasis but the exact susceptibility variation(s) have not yet been elucidated. Taken together, these findings convincingly demonstrate the important role of barrier dysfunction in various common skin disorders.     

Novel FLG null mutations in Korean patients with atopic dermatitis and comparison of the mutational spectra in Asian populations

Filaggrin is essential for the development of the skin barrier. Mutations in the gene encoding filaggrin have been identified as major predisposing factors for atopic disorders. Molecular analysis of the FLG gene in this study showed nine null and one unclassified mutation in 13 of 81 Korean patients with atopic dermatitis (AD): five novel null mutations (i.e. p.S1405*, c.5671_5672delinsTA, p.W1947*, p.G2025* and p.E3070*); four reported null mutations (i.e. c.3321delA, p.S1515*, p.S3296* and p.K4022*); and one unclassified mutation (i.e. c.306delAAAGCACAG). These variants are nonsense, premature termination codon or in‐frame deletion expected to cause loss‐of‐function of FLG. Genotype–phenotype correlation is not obvious in Korean AD patients with FLG null mutations. According to a review of the mutational spectra of the FLG gene in the Asian populations, FLG null mutations appeared to be unique in each population but some mutations such as p.R501*, c.3321delA, p.S1515*, p.S3296* and p.K4022* were commonly found in at least two of the selected Asian populations including Korean, Japanese, Chinese, Singaporean Chinese or Taiwanese. Further investigations on a larger group of Korean AD would be necessary to elucidate its clinical pathogenesis and mutational spectrum related to specific FLG null mutations for AD.     

TRP通道在炎症性皮肤病中的作用

瞬时受体电位(TRP)通道是一类非特异性阳离子通道蛋白家族,在皮肤感觉神经元和非神经元细胞中广泛表达,能被多种刺激激活,参与炎症性皮肤病的发生发展。本文重点对TRP通道的不同亚型在玫瑰痤疮、特应性皮炎、银屑病、接触性皮炎等炎症性皮肤病中的作用进行综述,提示TRP通道有望成为炎症性皮肤病的潜在治疗靶点。     

Expression of dipeptidyl-peptidase IV (CD26) on CD8+ T cells is significantly decreased in patients with psoriasis vulgaris and atopic dermatitis

T cells play a major role in inflammatory skin disorders such as psoriasis vulgaris and atopic dermatitis. They are both active on the level of cell-to-cell interaction and by the secretion of pro-inflammatory mediators. CD26 is a lymphocyte membrane-associated dipeptidyl peptidase IV (DPP IV), which is able to inactivate chemokines such as RANTES or eotaxin by cleaving dipeptides from the NH2-terminus of proteins. We investigated the expression of CD26 on CD4+ and CD8+ peripheral blood T cells in patients with psoriasis and atopic dermatitis. In addition PASI and SCORAD as a measure of disease severity were determined in each patient at the time of blood drawing. Thirty patients with psoriasis, 15 with atopic dermatitis and 17 age- and sex-matched healthy persons were investigated by two-colour flow cytometry using epitope-specific monoclonal antibodies. Our results revealed, that there is a significant decrease (P<0.05) of CD26 expression on CD8+ T cells in both psoriasis (7.7%+/-3.3, mean and SD, n=30) and atopic dermatitis patients (7.9%+/-3.7, mean and SD, n=15) compared to the control population (11.58%+/-5.0, mean and SD, n=17). However, there was no correlation to disease severity as determined by PASI and SCORAD, respectively. Since CD26 can be regarded as an anti-inflammatory principle the decreased expression in psoriasis and atopic dermatitis patients may lead to a dysbalance in favour of pro-inflammatory mediators in both clinical conditions.     

Urinary biomarker of oxidative stress in patients with psoriasis vulgaris and atopic dermatitis

Background  The involvement of oxidative stress in the pathogenesis of various skin disorders has been suggested for decades. However, few clinical studies have assessed oxidative stress in skin diseases. The easiest and least invasive method to assess oxidative stress in patients may be the measurement of oxidation products in urine.
Objective  This study aims to assess oxidative stress in psoriasis and atopic dermatitis patients.
Methods  Urine samples were collected from 29 psoriasis patients (25 males and 4 females), 21 atopic dermatitis patients (14 males and 7 females) and 20 healthy controls (16 males and 4 females). The severity and extent of psoriasis and atopic dermatitis was assessed by their area and severity index. We measured nitrate as a metabolite of nitric oxide, malondialdehyde as a major lipid oxidation product, and 8-hydroxydeoxyguanosine (8-OHdG) as a DNA oxidation marker.
Results  Urinary nitrate and 8-OHdG levels, but not malondialdehyde, were significantly higher in psoriasis patients than those in healthy controls. On the contrary, only urinary nitrate level was significantly higher in atopic dermatitis patients than those in healthy controls. The severity and extent of both psoriasis and atopic dermatitis significantly correlated with urinary nitrate level and malondialdehyde level, but it did not correlate with urinary 8-OHdG level.
Conclusions  Measurement of these three urinary oxidative products is non-invasive. Above all, measurement of urinary nitrate may be most useful in the clinical assessment of oxidative stress in both psoriasis and atopic dermatitis patients. There is a possibility that urinary 8-OHdG level may indicate the different pathogenesis between psoriasis and atopic dermatitis.