Aquaporin 3 and E-Cadherin Expression in Perilesional Vitiligo Skin.

Abstract

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.