Autoimmune blistering disease in a Pit Bull dog targets 180-kd skin

Abstract

Human bullous pemphigoid (BP) is an immune-mediated blistering disease characterized by autoantibodies against BP antigens (230/180 kd), which are constitutive glycoproteins of hemidesmosomes found in basal keratinocytes. Blistering diseases similar to human BP have been reported in dogs. IgG deposits at the basement membrane zone (BMZ) are a common feature of canine BP. Although circulating anti-BMZ IgG autoantibodies have been demonstrated in some cases of canine BP, the specific skin protein targeted by these autoantibodies has not been identified. In this study, we characterized the antigenic target of the autoantibodies in the serum from a 3-year-old castrated male Pit Bull Terrier with BP. Direct immunofluorescence of the patient's skin demonstrated IgG deposits at the dermal-epidermal junction. Indirect immunofluorescence demonstrated autoantibodies in the patient's serum that stained the epidermal roof of salt-split canine skin and left the dermal floor unstained. These serum autoantibodies did not stain normal intact dog skin but labeled intact bovine tongue. Direct immunoelectron microscopy of the dog's skin revealed IgG deposits within the hemidesmosomes of the basal keratinocytes. Western immunoblotting experiments showed that canine keratinocytes express both the 230-kd and 180-kd bullous pemphigoid antigens, and the autoantibodies from the patient's serum recognized the 180-kd bullous pemphigoid antigen in proteins extracted from canine and human keratinocytes. Canine BP has many parallel features with human BP including similar immune deposition of IgG within hemidesmosomes and a hemidesmosome-associated 180-kd glycoprotein target for circulating autoantibodies.