Epidermolysis bullosa acquisita (EBA) is an autoimmune sub-epidermal blistering disease characterized by
autoantibodies to type VII (anchoring fibril)
collagen. To date, however, direct evidence for a pathogenic role of human EBA
autoantibodies has not been demonstrated. In this study, we affinity-purified anti-
type VII collagen antibodies from EBA patients' sera and then injected them into adult hairless immunocompetent mice. Mice injected with EBA
autoantibodies developed skin fragility,
blisters, erosions, and nail loss on their paws - all features of EBA patients. By clinical, histological, immunological, and ultrastructural parameters, the induced lesions were reminiscent of human EBA. Histology showed
bullous lesions with an epidermal-dermal separation.
IgG and C3 deposits were observed at the epidermal-dermal junction. All mice had serum
antibodies that labeled the dermal side of
salt-split human skin like EBA sera. Direct immunogold electron microscopy specifically localized deposits of human
IgG to anchoring fibrils. (Fab')(2) fragments generated from EBA
autoantibodies did not induce disease. We conclude that EBA human patient
autoantibodies cause sub-epidermal
blisters and induce EBA skin lesions in mice. These passive transfer studies demonstrate that human EBA
autoantibodies are pathogenic. This novel EBA mouse model can be used to further investigate EBA autoimmunity and to develop possible
therapies.