Humoral Epitope Spreading in Autoimmune Bullous Diseases

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.

Dermatitis Herpetiformis and Celiac Disease Increase the Risk of Bullous Pemphigoid

“…Epitope spreading is a phenomenon in which an immune response is developed to one or more other epitopes in addition to the dominant epitope. It is known to exist in autoimmune bullous diseases, including BP (Chan et al, 1998;Didona and Di Zenzo, 2018). Epitope spreading has been reported to occur often during the first 3 months after a diagnosis of BP and is associated with disease severity (Di Zenzo et al, 2011).…”

“…Case reports of DH evolving into BP have been published (Ameen et al, 2000;Didona and Di Zenzo, 2018;Honeyman et al, 1972;Murphy et al, 2003), but larger studies of this probable association are currently lacking. The aim of the present study was to evaluate DH as a risk factor for BP in the setting of a Finnish nationwide registry-based case-control study.…”

Role of BP230 autoantibodies in bullous pemphigoid

“…Autoantibodies from patients with PNP can interact with several plakins, including desmoplakin, plectin, periplakin and envoplakin (Fig. a) . Intracellularly localized BP230 recognition is thought to occur secondarily after initial tissue damage.…”

“…1a). 41 Intracellularly localized BP230 recognition is thought to occur secondarily after initial tissue damage.…”

Bullous pemphigoid in 65 years old female: a case report

“…After binding of the autoantibodies to the target antigen, subepidermal bullae formation occurs through a series of events involving complement activation, recruitment of inflammatory cells (especially neutrophils and eosinophils), and the release of various chemokines and proteases, such as matrix metalloproteinases-9 (MMP-9) and neutrophil elastase. [8][9][10] In this case, the fluid examination and epidermal membrane examination was not performed due to low facility and cost to perform the examination. Consideration for the diagnosis was based on the clinical manifestation.…”