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

29.01.2012

Chiriac MT, Licarete E, Sas AG, Rados AM, Lupan I, Chiriac AM, Speth H, Pop-Vancia V, Domsa I, Sesarman A, Popescu O, Sitaru C.

Orphanet J Rare Dis. 2013;8:17

Orphanet J Rare Dis.        online article

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