A spontaneously arising porcine model of bullous pemphigoid

Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease ta rgeting the hemidesmosomal proteins bullous pemphigoid antigens 1 and 2, Cu rrently, there is no active animal model in which to dissect the immunopath ogenic mechanism, We noticed that cutaneous blistering arose spontaneously in 12 adult Yucatan minipigs, Skin lesions consisted of turgid, isolated or clustered vesicles that occasionally evolved from erythematous and pruriti c patches. Histopathological examination revealed subepidermal vesicles ric h in intact and degranulated eosinophils. Antigen mapping and transmission electron microscopy confirmed that dermoepidermal separation took place in the lamina lucida of the epidermal basement membrane zone, Direct immunoflu orescence revealed the presence of IgG deposited linearly at the dermoepide rmal junction in seven of nine skin specimens examined. Indirect immunofluo rescence testing confirmed the presence, in the serum from eight of eight a ffected pigs, of circulating basement membrane-specific IgG autoantibodies (titers 1:50 to 1:250), Using uncleaved and salt-split lip substrates, the autoantibodies were shown to target antigens situated not only at the basal , but also at the lateral and apical aspects of stratum basale keratinocyte s. Immunoelectron microscopy confirmed that circulating Ige autoantibodies recognized hemidesmosomal antigen(s). ELISA, immunoblotting and immunoadsor ption demonstrated that five of eight serum samples exhibited high immunore activity against BPAG2-NC16A peptides, This novel porcine acquired blisteri ng dermatosis could be proposed as a valuable model to conduct immunomechan istic studies on the natural progression of BP, correlation of autoreactive T cells or autoantibodies with disease activity, and the role of eosinophi ls in the blistering process, as these diseases cannot be modeled easily in human patients or in murine passive transfer models.