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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.

SUBMITTER: Csorba K 

PROVIDER: S-EPMC4196649 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Blister-inducing antibodies target multiple epitopes on collagen VII in mice.

Csorba Kinga K   Chiriac Mircea Teodor MT   Florea Florina F   Ghinia Miruna Georgiana MG   Licarete Emilia E   Rados Andreea A   Sas Alexandra A   Vuta Vlad V   Sitaru Cassian C  

Journal of cellular and molecular medicine 20140805 9


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 i  ...[more]

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