Abstract

Hailey-Hailey disease (HHD) is a rare genetic disorder characterized by blisters and erosions on intertriginous areas of the skin. It is related to a mutation of the ATP2C1 gene, which encodes a Ca2+ pump. It is characterized by multiple large foci of acantholysis in the epidermis, with dyskeratosis and suprabasilar clefting. Galectin-3 is a beta galactoside binding protein that plays an essential role in cell to cell and cell to matrix adhesion. We assessed galectin-3 immunohistochemical expression in HHD to explore its impact on the pathogenesis of this hereditary blistering disorder. We examined 11 consecutive specimens from 7 patients who were diagnosed with HHD. The specimen sections were stained by immunohistochemistry using anti-Galectin-3 antibody to evaluate the nuclear and cytoplasmic expression of galectin-3 around blisters and normal skin. We observed a significant decrease in keratinocyte cytoplasmic expression of galectin-3 around blisters (mean = 47.3% ± 2.3%) compared to the normal skin (mean = 82.7% ± 1.3%, p<0.0001) as well as keratinocyte nuclear expression around the blisters (mean = 40.0% ± 3.6%) compared to the normal skin (mean = 73.6% ± 1.9%, p<0.0001). While the initial acantholytic process in HHD is related to an abnormality in cadherin expression caused by altered Ca2+ pump concentration, lower expression of galectin-3 may cause the secondary extension of blisters by initiating cell to cell disassembly within the epidermis. Further investigations are required to explain the result of this difference on the disease pathogenesis.

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