Open AccessBlister‐inducing antibodies target multiple epitopes on collagen VII in mice
Author(s) -
Csorba Kinga,
Chiriac Mircea Teodor,
Florea Florina,
Ghinia Miruna Georgiana,
Licarete Emilia,
Rados Andreea,
Sas Alexandra,
Vuta Vlad,
Sitaru Cassian
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12338
Subject(s) - epidermolysis bullosa acquisita , epitope , autoantibody , antibody , in vivo , antigen , in silico , immunology , biology , microbiology and biotechnology , chemistry , biochemistry , gene
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 NC 2 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 NC 1 and NC 2 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 NC 1, but not NC 2 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 .