Expression of selected integrins and selectins in skin lesions in dermatitis herpetiformis

Abstract

Pathogenesis of skin lesions in DH is associated with destruction of basement membrane components. Autoantibodies binding to autoantigens localized in the basement membrane of the epidermis activate a series of immunological and enzymatic phenomena. Blister formation is initiated by accumulation of neutrophils, attracted by CD4+ T cells secreting mainly IFN-γ, TNF-α and IL-2, in dermal papillae, forming Pierrard's microabscesses. They are quickly transformed by oedema and inflammation into microvesicles and later into bigger subepidermal blisters. Adhesive molecules have an important role in processes of adhesion and interaction between individual cells as well as between cells and components of extracellular matrix. Selected integrins and selectins are cell surface transmembrane glycoproteins that function as adhesion receptors transmitting biochemical and mechanical signals in a bidirectional manner across the plasma membrane and thus influence most cellular functions such as proliferation, differentiation, apoptosis and cell migration during inflammation. The aim of the study was to investigate whether selected integrins and selectins are involved in pathogenesis of DH. Skin biopsies were taken from 13 patients with DH in an active stage of the disease and from 10 healthy subjects (controls). The localization and expression of integrins B1, B3 and B4 as well as selectins E and L were examined by immunohistochemistry (Novocastra). Signals for selected integrins were detected in basal keratinocytes in all the DH samples and in most of the samples focally in the other layers of epidermis. Neutrophils in microabscesses and perivascular infiltrations showed positive staining for integrins. Expression of beta 4 integrin in samples with blister was irregular and focal. Expression of selectins was detected mainly in basal keratinocytes in all DH samples and sometimes also in other keratinocytes. The strong expression of selectins was assessed in the vascular wall and in infiltrations. In all samples obtained from healthy volunteers weak expression of the examined molecules was detected in basal keratinocytes and endothelium cells. Our results allow us to conclude that integrins and selectins play an important role in the pathogenesis of skin lesions of DH.