Bakry Ola Ahmed, Hagag Magda Mostafa, Kandil Mona Abd El Halim, Shehata Wafaa Ahmed
Assistant Professor, Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufiya University , Egypt .
Professor, Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufiya University , Egypt .
J Clin Diagn Res. 2016 Dec;10(12):WC01-WC06. doi: 10.7860/JCDR/2016/22730.8959. Epub 2016 Dec 1.
Vitiligo is a common dermatologic disorder with debated aetiology. Most studies focused on role of melanocytes and few investigated the role of keratinocytes in pathogenesis of the disease.
To investigate the keratinocyte adhesion in perilesional vitiligo skin through the immunolocalization of Aquaporin-3 (AQP3) and E-cadherin.
Sixty five subjects were selected. These included 40 cases with vitiligo and 25 age and gender-matched healthy subjects as a control group.
Skin biopsies were taken from perilesional skin of cases and from site-matched areas of control subjects. The expression of AQP3 and E-cadherin was evaluated by immunohistochemical techniques.
Results were statistically analysed using IBM personal computer and the statistical package SPSS version 11. Fisher-exact and Chi-square tests were used to study the association between two qualitative variables. Mann-Whitney test was used for comparison between quantitative variables not normally distributed. Spearman's correlation coefficient was used to assess correlation between two quantitative variables. The p≤0.05 was considered significant.
Regarding AQP3 expression, strong intensity, diffuse distribution, higher percent of expression and higher H-score (p<0.001 for all) were significantly associated with control skin compared with perilesional skin in follicular and inter-follicular epidermis. Regarding E-cadherin expression, moderate intensity, higher percent of expression and higher H- score (p<0.001 for all) were significantly associated with control skin compared with perilesional skin in follicular and inter-follicular epidermis. No significant association was found between E-cadherin and AQP3 H-scores or percent of expression and clinical data of selected cases. No significant correlation was detected between E-cadherin and AQP3 H-scores or percent of expression and age of cases, disease duration or Vitiligo Disease Activity (VIDA) score.
The following sequence of events can be suggested for vitiligo pathogenesis, based on findings in perilesional skin: AQP3 is downregulated by a primary unknown factor and this will lead to down regulation of its downstream molecules, mainly phosphatidylinositol 3-kinase, E-cadherin and catenins, which is followed by defective keratinocyte adhesion and decreased release of keratinocyte-derived growth factors. Subsequently a secondary event, physical trauma, oxidative stress or autoantibodies, may lead to exfoliation of keratinocytes and pigmented cells.
白癜风是一种病因存在争议的常见皮肤病。大多数研究聚焦于黑素细胞的作用,很少有研究调查角质形成细胞在该疾病发病机制中的作用。
通过水通道蛋白3(AQP3)和E-钙黏蛋白的免疫定位研究白癜风皮损周围皮肤中角质形成细胞的黏附情况。
选取65名受试者。其中包括40例白癜风患者以及25名年龄和性别匹配的健康受试者作为对照组。
从病例的皮损周围皮肤以及对照受试者的相应部位取材进行皮肤活检。采用免疫组化技术评估AQP3和E-钙黏蛋白的表达。
使用IBM个人电脑及统计软件SPSS版本11对结果进行统计分析。采用Fisher精确检验和卡方检验研究两个定性变量之间的关联。采用曼-惠特尼检验对非正态分布的定量变量进行比较。采用斯皮尔曼相关系数评估两个定量变量之间的相关性。p≤0.05被认为具有统计学意义。
关于AQP3表达,在毛囊和毛囊间表皮中,与皮损周围皮肤相比,对照皮肤的AQP3表达强度强、呈弥漫性分布、表达百分比更高且H评分更高(所有p<0.001)。关于E-钙黏蛋白表达,在毛囊和毛囊间表皮中,与皮损周围皮肤相比,对照皮肤的E-钙黏蛋白表达强度中等、表达百分比更高且H评分更高(所有p<0.001)。在所选病例中,未发现E-钙黏蛋白与AQP3的H评分或表达百分比与临床数据之间存在显著关联。未检测到E-钙黏蛋白与AQP3的H评分或表达百分比与病例年龄、病程或白癜风疾病活动度(VIDA)评分之间存在显著相关性。
基于皮损周围皮肤的研究结果,可推测白癜风发病机制的以下事件序列:AQP3被一个未知的主要因素下调,这将导致其下游分子主要是磷脂酰肌醇3激酶、E-钙黏蛋白和连环蛋白下调,随后角质形成细胞黏附缺陷,角质形成细胞衍生生长因子释放减少。随后,第二个事件,即物理创伤、氧化应激或自身抗体,可能导致角质形成细胞和色素细胞脱落。