title: Blister-inducing antibodies target multiple epitopes on collagen VII in mice.
abstract: Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease of mucous membranes and the skin caused by autoantibodies against collagen VII. In silico and wet laboratory epitope mapping studies revealed numerous distinct epitopes recognized by EBA patients' autoantibodies within the non-collagenous (NC)1 and NC2 domains of collagen VII. However, the distribution of pathogenic epitopes on collagen VII has not yet been described. In this study, we therefore performed an in vivo functional epitope mapping of pathogenic autoantibodies in experimental EBA. Animals (n = 10/group) immunized against fragments of the NC1 and NC2 domains of collagen VII or injected with antibodies generated against the same fragments developed to different extent experimental EBA. Our results demonstrate that antibodies targeting multiple, distinct epitopes distributed over the entire NC1, but not NC2 domain of collagen VII induce blistering skin disease in vivo. Our present findings have crucial implications for the development of antigen-specific B- and T cell-targeted therapies in EBA.
authors.affiliation: Department of Dermatology, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.
authors.forename: Kinga
authors.initials: K
authors.lastname: Csorba
authors.forename: Mircea Teodor
authors.initials: MT
authors.lastname: Chiriac
authors.forename: Florina
authors.initials: F
authors.lastname: Florea
authors.forename: Miruna Georgiana
authors.initials: MG
authors.lastname: Ghinia
authors.forename: Emilia
authors.initials: E
authors.lastname: Licarete
authors.forename: Andreea
authors.initials: A
authors.lastname: Rados
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sas
authors.forename: Vlad
authors.initials: V
authors.lastname: Vuta
authors.forename: Cassian
authors.initials: C
authors.lastname: Sitaru
mesh_terms: D000818:Animals; D024143:Collagen Type VII / Q000276:immunology*; D016107:Epidermolysis Bullosa Acquisita / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005260:Female; D008297:Male; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012867:Skin / Q000276:immunology / Q000473:pathology
chemical_list: D024143:Collagen Type VII; D000939:Epitopes; D010446:Peptide Fragments
keywords: autoimmunity; collagen VII; epidermal basement membrane; functional epitope mapping
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