Experimental models of epidermolysis bullosa acquisita

Abstract

Epidermolysis bullosa acquisita (EBA) is an organspecific autoimmune disease with a well-defined antigenautoantibody system. Recently, mutually complementary ex vivo and animal models were developed for this disease. The blister formation of EBA can be reproduced by passively transferring antibodies against type VII collagen into mice. In addition, the Fc-dependent interaction of autoantibodies with granulocytes resulting in dermal-epidermal separation can be studied using patient autoantibodies and leukocytes from healthy donors in cryostat sections of normal human skin. Finally, the autoimmune response and the active blistering disease are replicated by immunizing mice with autologous type VII collagen. The results obtained using these experimental systems provided conclusive evidence that EBA is an antibody-mediated autoimmune disease. In addition, these models represent powerful new tools for understanding EBA pathophysiology and will likely offer unique opportunities to investigate the molecular mechanisms of antibody-mediated autoimmune diseases in general. Thus, due to improved disease modelling, EBA emerges as an exquisitely instructive model disease to study fundamental, biologically and clinically crucial aspects of antibody-mediated organ-specific autoimmune diseases that extend well beyond the limits of autoimmunity against type VII collagen. The new mechanistic insights gained from investigating EBA pathogenesis will facilitate the design of immunomodulatory interventions for this and other pathogenetically related organ-specific, antibody-dependent autoimmune diseases.

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

“…pidermolysis bullosa acquisita (EBA) is an organ-specific autoimmune disease characterized by subepidermal blisters and autoantibodies against type VII collagen, the main constituent of the anchoring fibrils at the dermal-epidermal junction (DEJ) (1,2). The pathogenic relevance of (auto)antibodies against type VII collagen has been conclusively demonstrated ex vivo and in experimental animals (3)(4)(5).…”

“…Although the blister formation induced by Abs against type VII collagen has been extensively investigated in patients and experimental animals both ex vivo and in vitro, the afferent phase of the specific autoimmune response in EBA, in particular the mechanisms of pathogenic autoantibody production, is poorly characterized (2). Autoantibodies against type VII collagen were extensively characterized in patients with EBA.…”

Granulocyte-dependent Autoantibody-induced Skin Blistering

“…Although several experimental settings, including ex vivo and animal models, are available for the autoimmune skin disease EBA 14 , by far the most suitable to study the granulocyte-dependent inflammatory pathways is the passive transfer of autoantibodies into animals. In contrast to the ex vivo model, where the granulocytes are added to the skin sections previously incubated with the autoantibodies 15 , here the infiltration of leukocytes is spontaneously reproduced by the mice.…”

Imunoglobulina intravenosa para tratamento de epidermólise bolhosa adquirida grave refratária a terapia imunossupressora convencional

“…1,2 It has an incidence of 0,2 per million of people, regardless race or sex. 3 There is association with allele HLA DR2, suggesting predisposition to EBA among carriers of this phenotype who are also more sensitive to bullous lupus. 4 The etiology is unknown although it is associated with the presence of antibodies against type VII collagen, main structural component of the anchorage fibrils of the dermo-epidermic junction, that could lead to a decrease in the number of anchorage fibrils.…”

“…1 The histologic analysis of the lesion shows subepidermic bulla, with varied dermic inflammatory infiltrate 1 The EBA is characterized with direct immunofluorescence, by the linear deposition of immunoreagents (deposits of IgG and C3) in the dermoepidermic junction. 1,3 The indirect immunofluorescence of the patient serum can show the antibodies. In the salt-split skin technique autoantibodies can be found on the dermic side, after artificial cleavage 6 .…”