Immunologic and histopathologic characterization of an active disease mouse model for pemphigus vulgaris

Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes that is caused by anti-desmoglein 3 IgG autoantibodies. Recently, we generated an active disease mouse model for pemphigus vulgaris by adoptive transfer of splenocytes from immunized desmoglein 3-/- mice to Rag2-/- mice. In this study, we performed immunologic and histopathologic studies using this pemphigus vulgaris model in mice and compared the gross and microscopic phenotypes of pemphigus vulgaris model mice and desmoglein 3-/- mice. Pemphigus vulgaris model mice showed strong in vivo IgG, and weak IgA deposition on keratinocyte cell surfaces in stratified squamous epithelia, and produced circulating anti-desmoglein 3 IgG antibodies without apparent cross-reactivity to desmoglein 1, in enzyme-linked immunosorbent assays. The predominant IgG subclass was IgG1. Pemphigus vulgaris model mice and desmoglein 3-/- mice were almost indistinguishable in terms of both gross and microscopic findings. Both types of mice showed suprabasilar acantholysis in the stratified squamous epithelia, including the oral mucous membranes and traumatized skin around the snout or paws; however, some pemphigus vulgaris model mice demonstrated a more severe phenotype than desmoglein 3-/- mice. The esophagus and forestomach were affected in some pemphigus vulgaris model mice, but not in desmoglein 3-/- mice. Furthermore, eosinophilic spongiosis, which is found in early pemphigus vulgaris lesions in patients, was observed in pemphigus vulgaris model mice but not in desmoglein 3-/- mice. Pemphigus vulgaris model mice reflect several of the histopathologic and immunologic features seen in pemphigus vulgaris patients, and provide a valuable tool to investigate the pathophysiologic mechanisms of pemphigus vulgaris.