Passive transfer of collagen XVII-specific antibodies induces sustained blistering disease in adult mice.
BACKGROUND
Bullous pemphigoid is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies directed mainly to the hemidesmosomal component collagen XVII. While recapitulating the main immunopathological features of the human disease, frank skin blistering does not develop in the absence of skin rubbing in experimental pemphigoid models that have been established in neonatal mice. Moreover, due to their experimental design they only allow for short-term disease observation. In the present study we aimed to establish a model that reproduces the frank skin blistering seen in patients and allows for longer observation times.


METHODS
Rabbit and sheep antibodies specific to several fragments of collagen XVII were generated and the purified antibodies were passively transferred into adult mice.


RESULTS
Collagen XVII-specific IgG bound to the basal membrane of the skin and mucous membranes activating murine complement in vivo. Mice injected with collagen XVII-specific antibodies, in contrast to mice receiving control antibodies, developed frank skin blistering disease, reproducing human bullous pemphigoid at the clinical, histological and immunopathological levels. Titres of circulating IgG in the serum of mice correlated with the extent of the clinical disease. Mice receiving sheep antibodies specific to murine collagen XVII showed an early onset and a more active disease when compared to litter mates receiving specific rabbit antibodies.


CONCLUSIONS
This novel animal model for bullous pemphigoid should facilitate further investigations of the pathogenesis of bullous pemphigoid and the development of innovative therapies for this disease.
Department of Biology, Babes-Bolyai University, Cluj-Napoca, Romania. mtchiriac@yahoo.com
Mircea Teodor
MT
Chiriac
Emilia
E
Licarete
Alexandra Gabriela
AG
Sas
Andreea Maria
AM
Rados
Iulia
I
Lupan
Anca Mirela
AM
Chiriac
Hilda
H
Speth
Vlad
V
Pop-Vancia
Iacob
I
Domsa
Alina
A
Sesarman
Octavian
O
Popescu
Cassian
C
Sitaru
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001768:Blister / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D024041:Non-Fibrillar Collagens / Q000276:immunology*; D000097805:Collagen Type XVII
D001323:Autoantibodies; D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII