Pemphigoid diseases are a group of autoimmune diseases defined by an autoantibody-induced immune response against distinct components of the hemidesmosomal anchoring complex at the dermal-epithelial junction (DEJ) of skin and mucous membranes with stratified epithelia, which are required for dermal-epithelial cohesion (1, 2). The group is constituted by bullous pemphigoid (BP), pemphigoid gestationis, membrane pemphigoid, mucous linear IgA disease, lichen planus pemphigoides, anti-p200 pemphigoid, and epidermolysis bullosa acquisita (EBA) (1). Pemphigoid diseases are chronic diseases with spontaneous exacerbations. Signature skin lesions are subepidermal blisters, developing into erosions and crusts. These can be ubiquitous or restricted to certain areas of the body skin surface and/or the mucous membranes (1).

BP is the most common pemphigoid disease and autoimmune blistering disease in Caucasians in general. Its incidence in the total population in Europe is estimated to be approx. 16-43/million/year,_ENREF_1_5 and in the group of elderly above 80 years its incidence is up to 330/million/year. Herein, its incidence has been sharply rising in recent decades (6, 7). The 1-year mortality rate of BP after first diagnosis is at 20 – 40%, which is the 2-3fold of age-matched peers (6-8). Treatment strategies for pemphigoid diseases predominantly resort to systemic immunosuppression by glucocorticoids, often causing serious adverse effects (1, 9, 10). There are only few clinical trials available on treatment regimens for pemphigoid diseases, and most treatment regimens are based on individual clinical experience (1, 11). Highly potent glucocorticosteroids can often moderate disease for a while, but in nearly 40% of all cases, disease relapses within 6 months after drug discontinuation (9).

The pathogenesis of pemphigoid diseases is complex and only incompletely understood. In the last decade, we have been significantly advancing this field, among others, by pioneering in the establishment of mouse models of pemphigoid diseases using adult mice. Previous models focused on neonatal mice, whose immune system is still immature. Furthermore, the models in neonatal mice can only be run over a short period of time, hence not reflecting the chronicity of pemphigoid disease, and are not suitable to test therapeutics. With our adult mouse models, we shed additional light on the pathomechanisms in pemphigoid disease laying ground for development of new therapeutic strategies (12, 13). Our unique mouse models are based on the induction of autoimmunity towards type XVII or type VII collagen and duplicate the clinical and immunopathological findings in the skin of BP patients and EBA patients with the inflammatory (BP-like) variant of the disease, respectively.

The skin is densely infiltrated by different immune cells, most abundantly neutrophils, but also eosinophils, T, and B cells (14-16). The phenotype in the EBA model clinically and histopathologically specifically mimics the inflammatory subtype of EBA, which in humans clinically and histopathologically strongly resembles BP (15, 17). For both, BP and the BP-like subtype of EBA, we have developed two variants of mouse models, with one variant based on the induction of autoimmunity directly in mice, consequently initiating autoantibody formation to type VII or type XVII collagen (“active EBA or BP”), and another model based on the transfer of anti-type VII or anti-type XVII collagen AAbs, previously induced in rabbits, into recipient mice (“AAb transfer EBA or BP”) (15, 16, 18-20). These mouse models are now instrumental to achieve the scientific goals of the CRU 303. In addition, the CRU 303 makes use of a large patient sample and information collection accumulated at the Department of Dermatology in Lübeck over the last 10 years. To extend this patient sample collection is a central part of the agenda of the CRU in order to facilitate the translation of our findings into clinical applications.