Autoantibodies to BPAG1e trigger experimental bullous pemphigoid in mice.

Makita, Eiko; Matsuzaki, Yasushi; Fukui, Tomohisa; Matsui, Akinobu; Minakawa, Satoko; Nakano, Hajime; Ito, Koichi; Kijima, Hiroshi; Sawamura, Daisuke

Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the hemidesmosomal proteins BP180 and BP230/bullous pemphigoid antigen 1e (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 BP models. We generated Bpag1 conditional knockout (Bpag1-cKO) mice, where the KO of Bpag1 is restricted to keratin 5-expressing epithelial cells. Bpag1-cKO 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.