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Induction of Complement-Fixing Autoantibodies against Type VII Collagen Results in Subepidermal Blistering in Mice¹

Cassian Sitaru^2,*, Mircea T. Chiriac^*, Sidonia Mihai^*, Jürgen Büning, Andreas Gebert, Akira Ishiko and Detlef Zillikens^*

^* Department of Dermatology, University of Lübeck, Lübeck, Germany; Department of Internal Medicine, University of Lübeck, Lübeck, Germany; Department of Anatomy, University of Lübeck, Lübeck, Germany; and Department of Dermatology, Keio University School of Medicine, Tokyo, Japan

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 FcRIIb-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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant Zi 439/6-2 (to D.Z. and C.S.) from the Deutsche Forschungsgemeinschaft.

² Address correspondence and reprint requests to Dr. Cassian Sitaru, Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. E-mail address: csitaru{at}fastmail.fm

³ Abbreviations used in this paper: EBA, epidermolysis bullosa acquisita; DEJ, dermal-epidermal junction; IF, immunofluorescence; NC, noncollagenous.

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