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Open Access Research

Passive transfer of collagen XVII-specific antibodies induces sustained blistering disease in adult mice

Mircea Teodor Chiriac12*, Emilia Licarete12, Alexandra Gabriela Sas2, Andreea Maria Rados2, Iulia Lupan12, Anca Mirela Chiriac3, Hilda Speth2, Vlad Pop-Vancia2, Iacob Domsa4, Alina Sesarman5, Octavian Popescu126 and Cassian Sitaru57*

Author Affiliations

1 Department of Biology, Babes-Bolyai University, Cluj-Napoca, Romania

2 Molecular Biology Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, Babes-Bolyai University, Cluj-Napoca, Romania

3 Medical Clinic III, University of Medicine and Pharmacy, Cluj-Napoca, Romania

4 Medical Clinic IV, University of Medicine and Pharmacy, Cluj-Napoca, Romania

5 Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany

6 Institute of Biology, Romanian Academy, Bucharest, Romania

7 Department of Dermatology, University of Freiburg, Freiburg, Germany

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Orphanet Journal of Rare Diseases 2013, 8:17  doi:10.1186/1750-1172-8-17

Published: 29 January 2013

Abstract

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.

Conclusion

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.

Keywords:
Autoimmunity; Collagen XVII; Inflammation; Skin