Induction of complement-fixing autoantibodies against type VII collagen results in subepidermal blistering in mice.
Experimental models reproducing an autoimmune response resulting in skin blistering in immunocompetent animals are lacking. Epidermolysis bullosa acquisita (EBA) is a bullous skin disease caused by autoantibodies to type VII collagen. In this study, we describe an active disease model of EBA by immunizing mice of different strains with murine type VII collagen. All mice developed circulating IgG autoantibodies that recognized type VII collagen and bound to the lamina densa of the dermal-epidermal junction. Importantly, subepidermal blisters developed in 82% of SJL-1, 56% of BALB/c mice, and 45% of Fc gammaRIIb-deficient mice, but not in SKH-1 mice. In susceptible animals, deposits of IgG1, IgG2, and complement C3 were detected at the dermal-epidermal junction. In contrast, in the nondiseased mice, tissue-bound autoantibodies were predominantly of the IgG1 subclass and complement activation was weak or absent. This active disease model reproduces in mice the clinical, histopathological, and immunopathological findings in EBA patients. This robust experimental system should greatly facilitate further studies on the pathogenesis of EBA and the development of novel immunomodulatory therapies for this and other autoimmune diseases.
Sitaru
Cassian
C
Department of Dermatology, University of Lübeck, Lübeck, Germany. csitaru@fastmail.fm
Chiriac
Mircea T
MT
Mihai
Sidonia
S
Büning
Jürgen
J
Gebert
Andreas
A
Ishiko
Akira
A
Zillikens
Detlef
D
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D001768:Blister / Q000276:immunology* / Q000473:pathology; D024143:Collagen Type VII / Q000276:immunology*; D004198:Disease Susceptibility; D016107:Epidermolysis Bullosa Acquisita / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology; D008297:Male; D051379:Mice; D010641:Phenotype
D001323:Autoantibodies; D024143:Collagen Type VII; D007074:Immunoglobulin G