Abstract

Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of their autoantibody targets has improved understanding of pathogenesis and laid the basis for the study of antigens/epitopes diversification, a process termed epitope spreading (ES). In this review, we have reported and discussed ES phenomena in autoimmune bullous diseases and underlined their functional role in disease pathogenesis. A functional ES has been proposed: (1) in bullous pemphigoid patients and correlates with the initial phase of the disease, (2) in pemphigus vulgaris patients with mucosal involvement during the clinical transition to a mucocutaneous form, (3) in endemic pemphigus foliaceus, underlining its role in disease pathogenesis, and (4) in numerous cases of disease transition associated with an intermolecular diversification of immune response. All these findings could give useful information to better understand autoimmune disease pathogenesis and to design antigen/epitope specific therapeutic approaches.

Highlights

  • Autoimmune diseases are caused by dysregulation of the immune system or arise as a consequence of microbial infection [1,2,3]

  • The difficulty to investigate epitope spreading (ES) in patients is probably due to the immunosuppressive treatments that could impair the diversification of the immune response and the time of ES appearance that, such as occurred in several mouse models, could become detectable before disease onset

  • Despite these limitations, in patients affected by autoimmune bullous diseases the functional role of ES has been demonstrated

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Summary

INTRODUCTION

Autoimmune diseases are caused by dysregulation of the immune system or arise as a consequence of microbial infection [1,2,3]. A subset of these antibodies had the potential to confer protection against rotavirus infection and to cause pathogenic effects on skin, suggesting a role of molecular mimicry in the disease pathogenesis [88] In this context, the authors speculate that even in the presence of non-pathogenic and cross-reactive antibodies, the activation of a cross-reactive B cell could stimulate Dsg3-reactive T cells to trigger a broader anti-Dsg B cell response, that react to other and possibly pathogenic epitopes leading to PV [88]. A strong relationship has been found between infestation with hematophagous insects, certain HLA susceptibility genes and the occurrence of fogo selvagem, suggesting a role of environmental factors in development of the disease [99] In accord with this idea, Qian et al have found in patients IgG4 and IgE autoantibodies that cross-reacted with a salivary antigen (LJM11) from sand flies targeting a shared conformational epitope in the EC1-EC2 subdomains [100]. Cutaneous lesions examinated by electron microscopy before and after the development of SLE

Method Note
Method
MMP who developed MCTD
LS 2 OLP 2 LS
Findings
CONCLUDING REMARKS
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