title: Repetitive immunization breaks tolerance to type XVII collagen and leads to bullous pemphigoid in mice.
abstract: Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease of the elderly associated with considerable morbidity and mortality. As unspecific immunosuppressants are still the mainstay of BP therapy, several animal models, based on the passive transfer of autoantibodies or immune cells, have been developed to obtain a better understanding of the pathogenesis of BP and evaluate novel therapeutic interventions. We describe in this study an experimental model inducing BP by immunization of immunocompetent mice with a recombinant form of the immunodominant 15th noncollagenous domain of murine BP180 (type XVII collagen). The homologous noncollagenous 16A domain of human BP180 has previously been identified as an immunodominant region in human BP. Immunization of female SJL/J mice with the murine peptide led to clinical disease within 14 wk in 56% of mice. In contrast, none of the other strains developed blisters despite the presence of autoantibodies. The clinical disease manifested for at least 8 wk without further manipulation. This novel immunization-induced model reflects key immunopathological characteristics of human BP, including binding of complement-fixing autoantibodies along the dermal-epidermal junction, elevated total IgE serum levels, and infiltration of skin lesions with eosinophilic granulocytes. The use of immunocompetent mice and the induction of sustained clinical disease not requiring additional interventions make this immunization-induced mouse model most suitable to further explore the pathogenesis of BP and novel therapeutic interventions for this and other autoantibody-mediated diseases.
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck D-23538, Germany.
authors.forename: Misa
authors.initials: M
authors.lastname: Hirose
authors.forename: Andreas
authors.initials: A
authors.lastname: Recke
authors.forename: Tina
authors.initials: T
authors.lastname: Beckmann
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiko
authors.forename: Katja
authors.initials: K
authors.lastname: Bieber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.forename: Enno
authors.initials: E
authors.lastname: Schmidt
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D001666:Binding Sites, Antibody; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D007108:Immune Tolerance / Q000235:genetics; D007117:Immunization, Secondary / Q000009:adverse effects; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D024041:Non-Fibrillar Collagens / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D010391:Pemphigoid, Bullous / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D007074:Immunoglobulin G; D024041:Non-Fibrillar Collagens; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome; D000097805:Collagen Type XVII