Abstract

Introduction: Autoimmune bullous skin diseases (ABDs) represent a group of disorders of the skin and mucosa commonly associated with deposits of immunoglobulins, complement and fibrinogen, and usually directed against distinct adhesion molecules. After studing these diseases for many years, we noted alterations not only between the cells junctions of the epidermis and/or the dermal/epidermal junction, but also in dermal skin appendageal structures and in mesenchymal tissue around the blisters. Based on our findings, we wanted to determine if the observed patterns of autoimmunity correlated with cutaneous vimentin expression. Materials and Methods: Archival biopsies previously diagnosed with ABDs by clinical, hematoxylin and eosin (H&E) and direct and/or immunofluorescence data were stained with antibodies directed against vimentin via immunohistochemistry (IHC). We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP), 20 with pemphigus vulgaris (PV), 8 with pemphigus foliaceus, 14 with dermatitis herpetiformis (DH) and 3 with Senear-Usher syndrome. Results: The H&E, DIF and vimentin patterns of positivity in the different ABDs confirmed that vimentin was compartmentalized around areas of dermal inflammation, around skin appendages and in epidermal, dermal and mesenchymal cell junction areas. Conclusion: Vimentin may be a useful tool for highlighting patterns of microenvironmental tissue alteration in multiple ABDs. The vimentin staining pattern observed was analogous to that we have previously described for proteases and protease inhibitors in patients affected by ABDs, expanding the concept that the autoimmune process extends beyond cell junctions.

Highlights

  • Autoimmune bullous skin diseases (ABDs) represent a group of disorders of the skin and mucosa commonly associated with deposits of immunoglobulins, complement and fibrinogen, and usually directed against distinct adhesion molecules

  • Vimentin is often utilized as a marker of mesenchymal-derived cells, or cells undergoing an epithelial-to-mesenchymal transition (EMT) during both normal development and metastatic progression [1,2,3,4,14]

  • Knowing that vimentin is useful for the identification of cells of mesenchymal origin in normal and neoplastic tissues, and based on our observed tissue “compartmentalization”, we suggest that rearrangement and/or sequestering of cells of mesenchymal origin occurs in the immune response in ABDs

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Summary

Introduction

Autoimmune bullous skin diseases (ABDs) represent a group of disorders of the skin and mucosa commonly associated with deposits of immunoglobulins, complement and fibrinogen, and usually directed against distinct adhesion molecules. After studing these diseases for many years, we noted alterations between the cells junctions of the epidermis and/or the dermal/epidermal junction, and in dermal skin appendageal structures and in mesenchymal tissue around the blisters. These antibodies, which have recently been shown to trigger complement activation, seem to be the source of acantholysis, the basic pathologic process of pemphigus [5,6,7,8,9,10]

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