Cross-reactivity of autoantibodies from patients with epidermolysis bullosa acquisita with murine collagen VII

• DOI: 10.1007/s00018-009-0256-3
• Publication Date: 2010-01-19T02:25:18Z
• Authors: Kinga Csorba; Alina Sesarman; Eva Oswald; Vasile Feldrihan; Anja Fritsch; Takashi Hashimoto; Cassian Sitaru
• Keywords: Adult; Aged, 80 and over; Keratinocytes; 0301 basic medicine; Collagen Type VII; Adolescent; Immunoblotting; Enzyme-Linked Immunosorbent Assay; Cross Reactions; Epidermolysis Bullosa Acquisita; Middle Aged; Recombinant Proteins; 3. Good health; Mice; 03 medical and health sciences; Immunoglobulin G; Animals; Humans; RNA, Messenger; Child; Fluorescent Antibody Technique, Indirect; Aged; Autoantibodies

The pathomechanism of antibody-mediated tissue damage in autoimmune diseases can be best studied in experimental models by passively transferring specific autoantibodies into animals. The reproduction of the disease in animals depends on several factors, including the cross-reactivity of patient autoantibodies with the animal tissue. Here, we show that autoantibodies from patients with epidermolysis bullosa acquisita (EBA), a subepidermal autoimmune blistering disease, recognize multiple epitopes on murine collagen VII. Indirect immunofluorescence microscopy revealed that EBA patients' IgG cross-reacts with mouse skin. Overlapping, recombinant fragments of murine collagen VII were used to characterize the reactivity of EBA sera and to map the epitopes on the murine antigen by ELISA and immunoblotting. The patients' autoantibody binding to murine collagen VII triggered pathogenic events as demonstrated by a complement fixing and an ex vivo granulocyte-dependent dermal-epidermal separation assay. These findings should greatly facilitate the development of improved disease models and novel therapeutic strategies.