Expression of protein components desmosomal apparatus and cytoskeleton of the epidermis in disease Hailey-Hailey

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Hailey-Hailey disease (benign familial chronic pemphigus Guzhero-Hailey-Hailey) - hereditary vesiculo-bullous dermatosis, where mutation of ATP2C1 gene results in morphological changes, which cause an abnormal location of molecules in intercellular adhesion. It is believed that the pathology may involve both the inner surface of the plasma membrane proteins of keratinocytes and desmosomal and adhesion molecules in epidermal intercellular connections. This present research provides the results of immunohistochemical study on the distribution of desmosomal cadherin (desmogleins 1, 2, 3), desmosomal proteins (plakoglobin, desmoplakin I, periplakin), intercellular junctions molecules (E-cadherin, cadherin complex) in desmosomal apparatus and cytoskeletal proteins (cytokeratins 5, 14, suprabasal layers of epidermis) in clinically intact and affected skin of patients with Hailey-Hailey disease. The research also detected violation in localization of the protein components in the system of intercellular junctions and the cytoskeleton from severe immunohistochemical reaction to disappearance and appearance in places not typical for its localization. Thus, the most severe expression of protein molecules was observed in the areas of acantholysis and the formation of intra-epidermal blisters with the penetration of specific material into the cytoplasm of keratinocytes and some acantholytic cells. Besides, in the clinically intact skin areas of patients the most intense damage (almost complete absence of expression or its “masking”) was identified as a damage with the cadherin adhesion molecules. The paradoxical phenomenon - intranuclear and/or perinuclear luminescence was marked by cytokeratin 5, desmogleins and cadherins. The complex mechanism of Hailey-Hailey disease involving various adhesion molecules and protein components of intercellular connections system requires ongoing detailed study of the expression of multiple adhesion molecules associated with the system of intercellular junctions. The acquired knowledge will bring understanding of the sequence of events in pathology (acantholysis) development and the identification of a number of additional differential diagnostic signs of Hailey-Hailey disease.

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About the authors

Natalie V. Makhneva

Moscow Regional Research and Clinical Institute

Moscow, 129110, Russian Federation
Department of dermato-venereology and dermato-oncology


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