Deciphering the Contribution of BP230 Autoantibodies in Bullous Pemphigoid

Abstract

Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease predominantly affecting elderly patients and carries significant morbidity and mortality. Patients typically suffer from severe itch with eczematous lesions, urticarial plaques, and/or tense blisters. BP is characterized by the presence of circulating autoantibodies against two components of the hemidesmosome, BP180 and BP230. The transmembrane BP180, also known as type XVII collagen or BPAG2, represents the primary pathogenic autoantigen in BP, whereas the intracellular BP230 autoantigen is thought to play a minor role in disease pathogenesis. Although experimental data exist suggesting that anti-BP230 antibodies are secondarily formed following initial tissue damage mediated by antibodies targeting extracellular antigenic regions of BP180, there is emerging evidence that anti-BP230 IgG autoantibodies alone directly contribute to tissue damage. It has been further claimed that a subset of patients has a milder variant of BP driven solely by anti-BP230 autoantibodies. Furthermore, the presence of anti-BP230 autoantibodies might correlate with distinct clinical features. This review summarizes the current understanding of the role of BP230 and anti-BP230 antibodies in BP pathogenesis.

Keywords: BP230; autoimmune blistering disease; bullous pemphigoid; dystonin; immunobullous disease.

Figure 1

Schematic of epidermal hemidesmosome. BP230 and plectin bind to keratin intermediate filaments. These subsequently complex with integrin α4β6 and BP180 (collagen 17). These then interact with laminin-332 in the lamina lucida. Antibodies are shown targeting the C-terminus of BP230 and the NC16a domain of BP180, which are most often targeted in bullous pemphigoid.