BP230 IgE autoantibodies in topical-steroid-resistant bullous pemphigoid.

BACKGROUND: IgE autoantibodies targeting BP230 can be identified in 38%-68% of bullous pemphigoid (BP) patients, yet the diagnostic and pathogenic value of anti-BP230 IgE still remains inconclusive. OBJECTIVE: We intend to investigate the clinical and immunological characteristics of anti-BP230 IgE in BP patients. METHODS AND RESULTS: Fifty-four BP patients were divided into two groups based on the responsiveness of a topical steroid. We investigated clinical features and IgE autoantibodies profiles by indirect immunofluorescence, ELISA and western blot between the two groups. BP disease area index (BPDAI) scores, total IgE, peripheral eosinophil counts, and anti-BP230 IgE level were significantly higher in the topical-steroid-resistant group. The majority of topical-steroid-resistant patients present with blister/erythematous phenotype (64.3%) and anti-BP230 IgE (59.5%), which correlates with total IgE levels. ELISAs of domain-specific BP230 recombinant proteins indicated that IgE in the topical-steroid-resistant group can react with all seven domains of BP230 and more frequently with the BP230-R1 epitope. CONCLUSION: Anti-BP230 IgE is more frequently observed in topical-steroid-therapy-resistant patients and the prefers R1 domain of BP230, which is not included in commercially available testing kits. Our study further suggests the pathogenic role of anti-BP230 IgE in BP. Performing anti-BP230 IgE detection can serve as an indicator for initiating systemic steroid therapy.

Role of BP230 autoantibodies in bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune disease associated with subepidermal blistering due to autoantibodies directed against BP180 and BP230. BP180 is currently considered as the major pathogenic autoantigen. However, previous clinical findings suggested that anti-BP230 autoantibodies alone can cause skin lesions in animal models and many BP patients. The characteristics of BP230 and the pathogenic roles of anti-BP230 antibodies have been proposed. First, at the molecular level, BP230 mediates the attachment of keratin intermediate filaments to the hemidesmosomal plaque and interacts with other constituents of hemidesmosomes. Second, the presence of BP230 autoantibodies may correlate with specific clinical features of BP. The immunoglobulin (Ig)G autoantibodies from BP patients react mainly against the C-terminus of BP230, while the IgE autoantibodies are still inconclusive. Third, in vivo, autoantibodies against BP230 involved in the disease may not only induce the inflammatory response but also impair the structural stability of hemidesmosomes. This article reviews recently published work about the role of BP230 and its antibodies, including IgG and IgE, aiming to find clues of its clinical association and lay the foundation for the research on the pathogenicity of antibodies against BP230.