Bullous Pemphigoid: A Focused Review on Antigen Epitopes

Abstract

Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease, characterized by autoantibodies against BP180 and BP230. Although the NC16A domain of BP180 is the immunodominant epitope, increasing evidence indicates that non-NC16A epitopes also contribute to the clinical heterogeneity of BP. This review summarizes the immunological characteristics and clinical significance of BP180 and BP230 epitopes, and discusses their associations with disease phenotypes, treatment responses, and prognosis. We also outline the pathogenesis and animal models of BP, and highlight the rarity of validated models for non-NC16A epitopes and their limited mechanistic scope. Emerging targeted therapies are critically reviewed in relation to current knowledge of epitope-specific immune responses. Although epitope profiling may eventually contribute to disease stratification and biomarker development, current evidence is insufficient to support routine epitope-guided therapeutic decision-making. Despite current progress, challenges remain in clarifying the pathogenicity of non-NC16A epitopes and establishing standardized detection. Future research should focus on epitope–phenotype correlations and large-cohort studies to promote the development of precision therapy for BP.