Autoantibodies to BPAG1e Trigger Experimental Bullous Pemphigoid in Mice.

Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the hemidesmosomal proteins BP180 and BP230/BPAG1e. Whereas the role of anti-BP180 antibodies has been extensively characterized, the pathogenicity of anti-BPAG1e antibodies remains unclear. The purpose of this study is to elucidate the role of antibodies to BPAG1e in the experimental bullous pemphigoid models. We generated Bpag1 conditional knockout mice, where the knockout of Bpag1 is restricted to keratin 5-expressing epithelial cells. Bpag1 conditional knockout mice were immunized with the C-terminal portion of BPAG1e, and the splenocytes were injected into Rag2-/- mice intravenously. The recipient mice presented with erosion on the feet and tails. Microscopic examination showed subepidermal blisters and a linear deposition of IgG at the dermal-epidermal junction. To assess the potential role of trauma on BP development, we inflicted surface wounds on the dorsum of the Rag2-/- recipient mice after adoptive transfer. The wounded Rag2-/- mice had increased morbidity and severity of BP-like symptoms. Moreover, the depletion of B cells from splenocytes abolished a subepidermal blistering phenotype in vivo. These findings demonstrate that antibodies to BPAG1e might play a pathogenic role in causing subepidermal blistering, and external factors, including trauma, might be a trigger for BP development.

Elderly-Onset Generalized Pustular Psoriasis without a Previous History of Psoriasis Vulgaris.

Generalized pustular psoriasis (GPP) is characterized by sudden fever and extensive erythema with pustules and occurs in patients with or without preceding psoriasis vulgaris. We report an 83-year-old man showing irregularly shaped erythema with pustules on the trunk and extremities. He initially had no fever and came to our clinic a few days after the onset of the skin lesions because of high fever and general malaise. We found an extension and new development of erythema and pustules on the whole body. The patient also manifested night delirium. Histological examination revealed neutrophil infiltration into the upper epidermis, which formed a spongiform pustule of Kogoj. Pustular fluid cultures were negative for bacteria. We diagnosed GPP without preceding psoriasis vulgaris. Mutation analysis revealed no significant mutations in IL36RN and CARD14. Previous reports indicated that onset of GPP at the age of 83 years is definitely rare. In older individuals, general disease characteristics include an atypical clinical course, an especially slow appearance and cure, and mental disorder. Our case also revealed such characteristics. Thus, it is necessary to be aware of the clinical course and mental problems in elderly patients with GPP.