A spontaneously arising porcine model of bullous pemphigoid

Abstract

Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease targeting the hemidesmosomal proteins bullous pemphigoid antigens 1 and 2. Currently, there is no active animal model in which to dissect the immunopathogenic 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 pruritic patches. Histopathological examination revealed subepidermal vesicles rich 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 immunofluorescence revealed the presence of IgG deposited linearly at the dermoepidermal junction in seven of nine skin specimens examined. Indirect immunofluorescence testing confirmed the presence, in the serum from eight of eight affected 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 keratinocytes. Immunoelectron microscopy confirmed that circulating IgG autoantibodies recognized hemidesmosomal antigen(s). ELISA, immunoblotting and immunoadsorption demonstrated that five of eight serum samples exhibited high immunoreactivity against BPAG2-NC16A peptides. This novel porcine acquired blistering dermatosis could be proposed as a valuable model to conduct immunomechanistic studies on the natural progression of BP, correlation of autoreactive T cells or autoantibodies with disease activity, and the role of eosinophils in the blistering process, as these diseases cannot be modeled easily in human patients or in murine passive transfer models.

T Cells Are Required for the Production of Blister-Inducing Autoantibodies in Experimental Epidermolysis Bullosa Acquisita

“…To validate our present results, these initial observations should be followed by more extensive descriptive investigation of the T cell autoimmune response in patients with EBA. Ideally, our findings should be confirmed using spontaneous models of EBA and other subepidermal autoimmune blistering diseases in animals (38)(39)(40)(41)(42)(43). Further characterizing the collagen-specific T cells in EBA should help developing therapeutic interventions aimed at re-establishing T cell tolerance and curbing the aberrant autoimmune response.…”

A Spontaneous Canine Model of Mucous Membrane (Cicatricial) Pemphigoid, an Autoimmune Blistering Disease Affecting Mucosae and Mucocutaneous Junctions

“…Five-micrometre skin sections were cut from paraffinembedded blocks, processed using routine methods, and stained with hematoxylin-eosin as well as Luna's stain for eosinophils [14]. Visualization of the lamina densa of the epidermal basement membrane was made either with periodic acid or Schiff (PAS) or after immunostaining with monoclonal antibodies specific for type IV collagen as described previously [10,15].…”

Chronological clinical and pathological documentation of porcine ulcerative dermatitis

“…However, the clinical and histopathological features of PUDS differ from PG and from porcine bullous pemphigoid (BP). Apoptosis, as seen in PUDS, is not described in either disease …”

“…No IgG deposits were detected using a direct immunofluorescence (IF) technique (goat anti‐porcine IgG‐Cy3, Chemicon International Inc.; Temecula, CA, USA) in any of the skin sections . Circulating IgG autoantibodies could not be demonstrated in two serum samples by an indirect IF method . Immunoreactivity against bullous pemphigoid antigen 2 (BPAG2‐NC16A) peptides was not detected in the serum samples …”