Evidence that anti-type VII collagen antibodies are pathogenic and responsible for the clinical, histological, and immunological features of epidermolysis bullosa acquisita.
Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease characterized by autoantibodies to type VII (anchoring fibril) collagen. Therefore, it is a prototypic autoimmune disease defined by a well-known autoantigen and autoantibody. In this study, we injected hairless immune competent mice with purified immunoglobulin G (IgG) fraction of serum from rabbits immunized with the non-collagenous amino-terminal domain (NC1) of human type VII collagen, the domain known to contain immunodominant epitopes. As a control, identical mice were injected with the IgG fraction of serum from non-immunized rabbits. Mice injected with immune IgG developed subepidermal skin blisters and erosions, IgG deposits at the epidermal-dermal junction of their skin, and circulating anti-NC1 antibodies in their serum-all features reminiscent of patients with EBA. Similar concentrations of control IgG purified from normal rabbits did not induce disease in the mice. These findings strongly suggest that autoantibodies that recognize human type VII collagen in EBA are pathogenic. This murine model, with features similar to the clinical, histological, and immunological features of EBA, will be useful for the fine dissection of immunopathogenic mechanisms in EBA and for the development of new therapeutic interventions.
Woodley
David T
DT
The Division of Dermatology, The Keck School of Medicine at the University of Southern California, Los Angeles, California 90033, USA. woodley@usc.edu
Chang
Carl
C
Saadat
Payam
P
Ram
Ramin
R
Liu
Zhi
Z
Chen
Mei
M
D000818:Animals; D001323:Autoantibodies / Q000633:toxicity*; D024143:Collagen Type VII / Q000276:immunology*; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000633:toxicity; D051379:Mice; D011817:Rabbits; D011994:Recombinant Proteins / Q000633:toxicity
D001323:Autoantibodies; D024143:Collagen Type VII; D007074:Immunoglobulin G; D011994:Recombinant Proteins