IgE-mediated mechanisms in bullous pemphigoid and other autoimmune bullous diseases

Abstract

Autoimmune bullous diseases (AIBDs) are characterized by autoantibodies against structural proteins of the dermal-epidermal junction (in pemphigoid diseases) and the epidermal/ epithelial desmosomes (in pemphigus diseases). By far, the most common AIBD is bullous pemphigoid, which is immunopathologically characterized by autoantibodies against BP180 (type XVII collagen) and BP230. IgG and, to a lesser extent, IgA autoantibodies are the major autoantibody isotypes in these disorders. IgE autoantibodies are increasingly reported in particular in bullous pemphigoid. The development of specific and sensitive anti-BP180 IgE ELISA systems, the report of two experimental murine models employing IgE autoantibodies against BP180, and the successful treatment of bullous pemphigoid with the anti-IgE antibody omalizumab have raised interest in the role of IgE autoantibodies and the modulation of their production in AIBDs. Here, the relevance of IgE autoantibodies in the diagnosis, pathophysiology, and treatment decisions of AIBDs, with a focus on bullous pemphigoid, is reviewed. ARTICLE HISTORY

Peripheral eosinophilia in bullous pemphigoid: prevalence and influence on the clinical manifestation

“…It has been suggested that this degranulation occurs gradually, 17,24 hence contributing to blister formation. 25 Moreover, gelatinase derived from eosinophils has been reported to cleave the extracellular domain of BP180. 26 Peripheral eosinophilia has been reported in 50-60% of patients with BP in two uncontrolled retrospective cohort studies, 27,28 and is positively correlated with disease severity and time until the start of the consolidation phase.…”

Immune response patterns in non‐communicable inflammatory skin diseases

“…The contribution of other lymphocytes such as follicular helper T cells to pathogenic antibody formation in bullous skin diseases is currently under debate. 18 IgG, IgA or IgE 19 antibodies directed against structural proteins of the skin elicit the bullous pattern. They may either directly lead to keratinocyte apoptosis and loss of cellular adhesion, a concept called apoptolysis, 20 or bind to their target and cause secondary inflammation via opsonization.…”

Skin-Associated B Cells in Health and Inflammation

“…Recently, B cells are increasingly recognized as an important part of the infiltrating immune compartment in autoimmune and inflammatory skin diseases. B cell numbers are elevated in lesional skin relative to control skin specimens in a number of inflammatory diseases, including, but not limited to, psoriasis (47), pemphigus (18), lupus profundus (19,20), systemic sclerosis (scleroderma) (48), discoid lupus erythematosus (49,50), Sjögren's syndrome (51), IgG4related skin diseases (33,34), atopic dermatitis (52), and allergic contact dermatitis (53). Although an increase in skininfiltrating B cells already suggested a role for B cells in cutaneous inflammation, the therapeutic success of systemic B cell depletion with rituximab confirmed a pathogenic role for B cells in a number of these diseases (54)(55)(56).…”