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.

KEYWORDS:

• Bullous pemphigoid
• BP180
• BP230
• ELISA
• eosinophilia
• immunofluorescence microscopy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Total IgE levels and the soluble FcεRII are elevated in BP.

• Total IgE levels correlate with disease activity, levels of IL-5, and eosinophilic cationic protein.

• Eosinophilia is a typical feature of BP with elevated levels of eosinophil chemotactic factor and myeloperoxidase.

• Deposits of IgE in human skin have been found along the BMZ in patients with BP and mucous membrane pemphigoid.

• BP180-specific IgE autoantibodies are mainly directed against the NC16A domain.

• BP180 NC16A-specific IgE autoantibodies correlate with disease severity in BP

• BP230-specific IgE autoantibodies are variably found in BP.

• The successful use of the anti-IgE antibody omalizumab in individual patients with BP points toward a pathogenic role of IgE autoantibodies in this disease.

• Several in vitro approaches and two mouse models suggest a pathogenically relevant role of anti-BP180 IgE in the early phase of BP.