Experimental animal models of bullous pemphigoid

Bullous pemphigoid (BP) is a cutaneous autoimmune blistering disease characterized immunohistologically by dermal-epidermal junction separation, an inflammatory cell infiltrate in the upper dermis, and autoantibodies directed against the hemidesmosomal proteins BP230 and BP180. A passive transfer mouse model of BP that uses rabbit antibodies targeted against murine BP180 reproduces the key clinical and histological features of human BP. Using this model, it has been demonstrated that subepidermal blistering is initiated by anti-BP180 antibodies and mediated by complement activation, mast cell degranulation, neutrophil infiltration, and proteinase secretion. The rabbit-anti mouse IgG passive transfer model is not compatible with study of human pathogenic antibodies, as the human and murine antigenic epitopes are not cross-reactive. Two humanized mouse models in which the murine form of BP180 is replaced the human homologue have recently emerged. Autoantibodies isolated from human patients induce experimental BP in the humanized mice, and disease progression mirrors that observed in the rabbit-anti mouse IgG model. The humanized mouse models present ideal in vivo systems to test novel therapeutic strategies for disease management. In this review, we discuss the progress made in understanding the pathogenesis of BP, as well as the limits of using animal models to investigate human disease.